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Hao-Fountain syndrome protein USP7 controls neuronal differentiation via BCOR–ncPRC1.1 Genes Dev. (IF 7.5) Pub Date : 2025-02-07 Joyce Wolf van der Meer, Axelle Larue, Jan A. van der Knaap, Gillian E. Chalkley, Ayestha Sijm, Leila Beikmohammadi, Elena N. Kozhevnikova, Aniek van der Vaart, Ben C. Tilly, Karel Bezstarosti, Dick H.W. Dekkers, Wouter A.S. Doff, P. Jantine van de Wetering-Tieleman, Kristina Lanko, Tahsin Stefan Barakat, Tim Allertz, Jeffrey van Haren, Jeroen A.A. Demmers, Yaser Atlasi, C. Peter Verrijzer
Pathogenic variants in the ubiquitin-specific protease 7 (USP7) gene cause a neurodevelopmental disorder called Hao-Fountain syndrome. However, it remains unclear which of USP7's pleiotropic functions are relevant for neurodevelopment. Here, we present a combination of quantitative proteomics, transcriptomics, and epigenomics to define the USP7 regulatory circuitry during neuronal differentiation.
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The double life of mammalian DNA replication origins Genes Dev. (IF 7.5) Pub Date : 2025-02-04 Olivier Hyrien, Guillaume Guilbaud, Torsten Krude
Mammalian DNA replication origins have been historically difficult to identify and their determinants are still unresolved. Here, we first review methods developed over the last decades to map replication initiation sites either directly via initiation intermediates or indirectly via determining replication fork directionality profiles. We also discuss the factors that may specify these sites as replication
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A feedback amplifier circuit with Notch and E2A orchestrates T-cell fate and suppresses the innate lymphoid cell lineages during thymic ontogeny Genes Dev. (IF 7.5) Pub Date : 2025-02-04 Kazuko Miyazaki, Kenta Horie, Hitomi Watanabe, Reiko Hidaka, Rinako Hayashi, Norihito Hayatsu, Kentaro Fujiwara, Rei Kuwata, Takuya Uehata, Yotaro Ochi, Makoto Takenaka, Risa Karakida Kawaguchi, Koichi Ikuta, Osamu Takeuchi, Seishi Ogawa, Katsuto Hozumi, Georg A. Holländer, Gen Kondoh, Taishin Akiyama, Masaki Miyazaki
External signals from the thymic microenvironment and the activities of lineage-specific transcription factors (TFs) instruct T-cell versus innate lymphoid cell (ILC) fates. However, mechanistic insights into how factors such as Notch1–Delta-like-4 (Dll4) signaling and E-protein TFs collaborate to establish T-cell identity remain rudimentary. Using multiple in vivo approaches and single-cell multiome
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Corrigendum: Identification of a PTEN-regulated STAT3 brain tumor suppressor pathway Genes Dev. (IF 7.5) Pub Date : 2025-02-01 Núria de la Iglesia, Genevieve Konopka, Sidharth V. Puram, Jennifer A. Chan, Robert M. Bachoo, Mingjian J. You, David E. Levy, Ronald A. DePinho, Azad Bonni
Genes & Development 22: 449–462 (2008)
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LINE1 elements at distal junctions of rDNA repeats regulate nucleolar organization in human embryonic stem cells Genes Dev. (IF 7.5) Pub Date : 2025-02-01 Lamisa Ataei, Juan Zhang, Simon Monis, Krystyna Giemza, Kirti Mittal, Joshua Yang, Mayu Shimomura, Brian McStay, Michael D. Wilson, Miguel Ramalho-Santos
The nucleolus is a major subnuclear compartment where ribosomal DNA (rDNA) is transcribed and ribosomes are assembled. In addition, recent studies have shown that the nucleolus is a dynamic organizer of chromatin architecture that modulates developmental gene expression. rDNA gene units are assembled into arrays located in the p-arms of five human acrocentric chromosomes. Distal junctions (DJs) are
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E3 ligase substrate adaptor SPOP fine-tunes the UPR of pancreatic β cells Genes Dev. (IF 7.5) Pub Date : 2025-02-01 Alexis U. Oguh, Matthew W. Haemmerle, Sabyasachi Sen, Andrea V. Rozo, Shristi Shrestha, Jean-Philippe Cartailler, Hossein Fazelinia, Hua Ding, Sam Preza, Juxiang Yang, Xiaodun Yang, Lori Sussel, Juan R. Alvarez-Dominguez, Nicolai Doliba, Lynn A. Spruce, Rafael Arrojo e Drigo, Doris A. Stoffers
The Cullin-3 E3 ligase adaptor protein SPOP targets proteins for ubiquitination and proteasomal degradation. We previously established the β-cell transcription factor (TF) and human diabetes gene PDX1 as an SPOP substrate, suggesting a functional role for SPOP in the β cell. Here, we generated a β-cell-specific Spop deletion mouse strain (SpopβKO) and found that Spop is necessary to prevent aberrant
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NKX2.2 and KLF4 cooperate to regulate α-cell identity Genes Dev. (IF 7.5) Pub Date : 2025-02-01 Elliott P. Brooks, McKenna R. Casey, Kristen L. Wells, Tsung-Yun Liu, Madeline Van Orman, Lori Sussel
Transcription factors (TFs) are indispensable for maintaining cell identity through regulating cell-specific gene expression. Distinct cell identities derived from a common progenitor are frequently perpetuated by shared TFs, yet the mechanisms that enable these TFs to regulate cell-specific targets are poorly characterized. We report that the TF NKX2.2 is critical for the identity of pancreatic islet
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Transcriptional regulation of the piRNA pathway by Ovo in animal ovarian germ cells Genes Dev. (IF 7.5) Pub Date : 2025-02-01 Azad Alizada, Gregory J. Hannon, Benjamin Czech Nicholson
The gene-regulatory mechanisms controlling the expression of the germline PIWI-interacting RNA (piRNA) pathway components within the gonads of metazoan species remain largely unexplored. In contrast to the male germline piRNA pathway, which in mice is known to be activated by the testis-specific transcription factor A-MYB, the nature of the ovary-specific gene-regulatory network driving the female
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Alternative splicing controls pan-neuronal homeobox gene expression Genes Dev. (IF 7.5) Pub Date : 2025-02-01 Eduardo Leyva-Díaz, Michael Cesar, Karinna Pe, José Ignacio Jordá-Llorens, Jessica Valdivia, Oliver Hobert
The pan-neuronally expressed and phylogenetically conserved CUT homeobox gene ceh-44/CUX orchestrates pan-neuronal gene expression throughout the nervous system of Caenorhabditis elegans. As in many other species, including humans, ceh-44/CUX is encoded by a complex locus that also codes for a Golgi-localized protein, called CASP (Cux1 alternatively spliced product) in humans and CONE-1 (“CASP of nematodes”)
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Metabolic regulation in adult and aging skeletal muscle stem cells Genes Dev. (IF 7.5) Pub Date : 2025-02-01 Vittorio Sartorelli, Veronica Ciuffoli
Adult stem cells maintain homeostasis and enable regeneration of most tissues. Quiescence, proliferation, and differentiation of stem cells and their progenitors are tightly regulated processes governed by dynamic transcriptional, epigenetic, and metabolic programs. Previously thought to merely reflect a cell's energy state, metabolism is now recognized for its critical regulatory functions, controlling
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LINE-1, the NORth star of nucleolar organization Genes Dev. (IF 7.5) Pub Date : 2025-02-01 Misaki Matsuo, Gael Cristofari
Long interspersed element-1 (LINE-1) retrotransposons are abundant transposable elements in mammals and significantly influence chromosome structure, chromatin organization, and 3D genome architecture. In this issue of Genes & Development, Ataei et al. (doi:10.1101/gad.351979.124) identify a homininae-specific LINE-1 element within nucleolar organizer regions (NORs) that is specifically transcribed
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Histone bivalency in CNS development Genes Dev. (IF 7.5) Pub Date : 2025-01-29 Kärt Mätlik, Eve-Ellen Govek, Mary E. Hatten
Neuronal maturation is guided by changes in the chromatin landscape that control developmental gene expression programs. Histone bivalency, the co-occurrence of activating and repressive histone modifications, has emerged as an epigenetic feature of developmentally regulated genes during neuronal maturation. Although initially associated with early embryonic development, recent studies have shown that
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The Rbfox1/LASR complex controls alternative pre-mRNA splicing by recognition of multipart RNA regulatory modules Genes Dev. (IF 7.5) Pub Date : 2025-01-29 Parham Peyda, Chia-Ho Lin, Kelechi Onwuzurike, Douglas L. Black
The Rbfox proteins regulate alternative pre-mRNA splicing by binding to the RNA element GCAUG. In the nucleus, most of Rbfox is bound to the large assembly of splicing regulators (LASR), a complex of RNA-binding proteins that recognize additional RNA motifs. However, it remains unclear how the different subunits of the Rbfox/LASR complex act together to bind RNA and regulate splicing. We used a nuclease
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Two unrelated distal genes activated by a shared enhancer benefit from localizing inside the same small topological domain Genes Dev. (IF 7.5) Pub Date : 2025-01-27 Yike Huang, Marjon J.A.M. Verstegen, Sjoerd J.D. Tjalsma, Peter H.L. Krijger, Kavvya Gupta, Minhee Park, Alistair Boettiger, Wouter de Laat
Enhancers are tissue-specific regulatory DNA elements that can activate transcription of genes over distance. Their target genes most often are located in the same contact domain—chromosomal entities formed by cohesin DNA loop extrusion and typically flanked by CTCF-bound boundaries. Enhancers shared by multiple unrelated genes are underexplored but may be more common than anticipated. Here, we analyzed
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ESRP2–microRNA-122 axis promotes the postnatal onset of liver polyploidization and maturation Genes Dev. (IF 7.5) Pub Date : 2025-01-10 Sushant Bangru, Jackie Chen, Nicholas Baker, Diptatanu Das, Ullas V. Chembazhi, Jessica M. Derham, Sandip Chorghade, Waqar Arif, Frances Alencastro, Andrew W. Duncan, Russ P. Carstens, Auinash Kalsotra
Hepatocyte polyploidy and maturity are critical to acquiring specialized liver functions. Multiple intracellular and extracellular factors influence ploidy, but how they cooperate temporally to steer liver polyploidization and maturation or how post-transcriptional mechanisms integrate into these paradigms is unknown. Here, we identified an important regulatory hierarchy in which postnatal activation
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Genes & Development aims for an expansive horizon Genes Dev. (IF 7.5) Pub Date : 2025-01-01 Andrew Dillin
Dear Colleagues,
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Genes & Development: an evolution Genes Dev. (IF 7.5) Pub Date : 2025-01-01 John R. Inglis
With this first Genes & Development issue of 2025, it is my great pleasure to welcome new editorial leadership to the journal.
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Forcing the code: tension modulates signaling to drive morphogenesis and malignancy Genes Dev. (IF 7.5) Pub Date : 2025-01-01 Radhika Narain, Jonathon M. Muncie-Vasic, Valerie M. Weaver
Development and disease are regulated by the interplay between genetics and the signaling pathways stimulated by morphogens, growth factors, and cytokines. Experimental data highlight the importance of mechanical force in regulating embryonic development, tissue morphogenesis, and malignancy. Force not only sculpts tissue movements to drive embryogenesis and morphogenesis but also modifies the context
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“Undruggable KRAS”: druggable after all Genes Dev. (IF 7.5) Pub Date : 2025-01-01 Adrienne D. Cox, Channing J. Der
The three RAS genes (HRAS, KRAS, and NRAS) comprise the most frequently mutated oncogene family in cancer. KRAS is the predominant isoform mutated in cancer and is most prevalently mutated in major causes of cancer deaths including lung, colorectal, and pancreatic cancers. Despite extensive academic and industry efforts to target KRAS, it would take nearly four decades before approval of the first
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mTORC1, the maestro of cell metabolism and growth Genes Dev. (IF 7.5) Pub Date : 2025-01-01 Long He, Sungyun Cho, John Blenis
The mechanistic target of rapamycin (mTOR) pathway senses and integrates various environmental and intracellular cues to regulate cell growth and proliferation. As a key conductor of the balance between anabolic and catabolic processes, mTOR complex 1 (mTORC1) orchestrates the symphonic regulation of glycolysis, nucleic acid and lipid metabolism, protein translation and degradation, and gene expression
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BRCA1 and BRCA2: from cancer susceptibility to synthetic lethality Genes Dev. (IF 7.5) Pub Date : 2025-01-01 Anna Khalizieva, Sarah C. Moser, Peter Bouwman, Jos Jonkers
The discovery of BRCA1 and BRCA2 as tumor susceptibility genes and their role in genome maintenance has transformed our understanding of hereditary breast and ovarian cancer. This review traces the evolution of BRCA1/2 research over the past 30 years, highlighting key discoveries in the field and their contributions to tumor development. Additionally, we discuss current preventive measures for BRCA1/2
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Genetics and biology of pancreatic ductal adenocarcinoma Genes Dev. (IF 7.5) Pub Date : 2025-01-01 Haoqiang Ying, Alec C. Kimmelman, Nabeel Bardeesy, Raghu Kalluri, Anirban Maitra, Ronald A. DePinho
Pancreatic ductal adenocarcinoma (PDAC) poses a grim prognosis for patients. Recent multidisciplinary research efforts have provided critical insights into its genetics and tumor biology, creating the foundation for rational development of targeted and immune therapies. Here, we review the PDAC genomic landscape and the role of specific oncogenic events in tumor initiation and progression, as well
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Deciphering normal and cancer stem cell niches by spatial transcriptomics: opportunities and challenges Genes Dev. (IF 7.5) Pub Date : 2025-01-01 Hirak Sarkar, Eunmi Lee, Sereno L. Lopez-Darwin, Yibin Kang
Cancer stem cells (CSCs) often exhibit stem-like attributes that depend on an intricate stemness-promoting cellular ecosystem within their niche. The interplay between CSCs and their niche has been implicated in tumor heterogeneity and therapeutic resistance. Normal stem cells (NSCs) and CSCs share stemness features and common microenvironmental components, displaying significant phenotypic and functional
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Molecular and cellular dynamics of squamous cell carcinomas across tissues Genes Dev. (IF 7.5) Pub Date : 2025-01-01 Matthew R. Kudelka, Yonit Lavin, Siman Sun, Elaine Fuchs
Squamous cell carcinomas (SCCs), arising from the skin, head and neck, lungs, esophagus, and cervix, are collectively among the most common cancers and a frequent cause of cancer morbidity and mortality. Despite distinct stratified epithelial tissues of origin, converging evidence points toward shared biologic pathways across SCCs. With recent breakthroughs in molecular technologies have come novel
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Arrested development: the dysfunctional life history of medulloblastoma Genes Dev. (IF 7.5) Pub Date : 2025-01-01 Ran Tao, Katie Han, Stephanie C. Wu, Jake D. Friske, Martine F. Roussel, Paul A. Northcott
Medulloblastoma is a heterogeneous embryonal tumor of the cerebellum comprised of four distinct molecular subgroups that differ in their developmental origins, genomic landscapes, clinical presentation, and survival. Recent characterization of the human fetal cerebellum at single-cell resolution has propelled unprecedented insights into the cellular origins of medulloblastoma subgroups, including those
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Reviewers, Volume 38 (2024) Genes Dev. (IF 7.5) Pub Date : 2024-11-01
The editors would like to thank the Editorial Board and the following scientists who reviewed papers and provided advice during 2024.
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Corrigendum: Functional rejuvenation of aged neural stem cells by Plagl2 and anti-Dyrk1a activity Genes Dev. (IF 7.5) Pub Date : 2024-11-01 Takashi Kaise, Masahiro Fukui, Risa Sueda, Wenhui Piao, Mayumi Yamada, Taeko Kobayashi, Itaru Imayoshi, Ryoichiro Kageyama
Genes & Development 36: 23–37 (2022)
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PROSER1 modulates DNA demethylation through dual mechanisms to prevent syndromic developmental malformations Genes Dev. (IF 7.5) Pub Date : 2024-11-01 Anna Fleming, Elena V. Knatko, Xiang Li, Ansgar Zoch, Zoe Heckhausen, Stephanie Stransky, Alejandro J. Brenes, Simone Sidoli, Petra Hajkova, Dónal O'Carroll, Kasper D. Rasmussen
The link between DNA methylation and neurodevelopmental disorders is well established. However, how DNA methylation is fine-tuned—ensuring precise gene expression and developmental fidelity—remains poorly understood. PROSER1, a known TET2 interactor, was recently linked to a severe neurodevelopmental disorder. Here, we demonstrate that PROSER1 interacts with all TET enzymes and stabilizes chromatin-bound
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Evidence for dual roles of histone H3 lysine 4 in antagonizing Polycomb group function and promoting target gene expression Genes Dev. (IF 7.5) Pub Date : 2024-11-01 Cyril S. Anyetei-Anum, Mary P. Leatham-Jensen, Geoffrey C. Fox, B. Rutledge Smith, Venkat R. Chirasani, Krzysztof Krajewski, Brian D. Strahl, Jill M. Dowen, A. Gregory Matera, Robert J. Duronio, Daniel J. McKay
Tight control over cell identity gene expression is necessary for proper adult form and function. The opposing activities of Polycomb and trithorax complexes determine the on/off state of cell identity genes such as the Hox factors. Polycomb group complexes repress target genes, whereas trithorax group complexes are required for their expression. Although trithorax and its orthologs function as methyltransferases
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Proteomic insights into circadian transcription regulation: novel E-box interactors revealed by proximity labeling Genes Dev. (IF 7.5) Pub Date : 2024-11-01 Manon Torres, Marieluise Kirchner, Caroline G. Marks, Philipp Mertins, Achim Kramer
Circadian clocks (∼24 h) are responsible for daily physiological, metabolic, and behavioral changes. Central to these oscillations is the regulation of gene transcription. Previous research has identified clock protein complexes that interact with the transcriptional machinery to orchestrate circadian transcription, but technological constraints have limited the identification of de novo proteins.
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Classifying the molecular functions of transcription factors beyond activation and repression Genes Dev. (IF 7.5) Pub Date : 2024-11-01 Jinhong Dong, Michael J. Guertin
Notch signaling is a highly conserved pathway activated by dynamic cellular interactions that initiates a molecular cascade that ultimately drives changes in gene expression. The Notch transcriptional complex (NTC) regulates genes that influence development and homeostasis. In this issue of Genes & Development, Rogers and colleagues (doi:10.1101/gad.352108.124) leverage a rapid Notch activation system
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DNA-directed termination of mammalian RNA polymerase II Genes Dev. (IF 7.5) Pub Date : 2024-11-01 Lee Davidson, Jérôme O. Rouvière, Rui Sousa-Luís, Takayuki Nojima, Nicholas J. Proudfoot, Torben Heick Jensen, Steven West
The best-studied mechanism of eukaryotic RNA polymerase II (RNAPII) transcriptional termination involves polyadenylation site-directed cleavage of the nascent RNA. The RNAPII-associated cleavage product is then degraded by XRN2, dislodging RNAPII from the DNA template. In contrast, prokaryotic RNAP and eukaryotic RNAPIII often terminate directly at T-tracts in the coding DNA strand. Here, we demonstrate
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Chronic interferon-stimulated gene transcription promotes oncogene-induced breast cancer Genes Dev. (IF 7.5) Pub Date : 2024-11-01 Hexiao Wang, Claudia Canasto-Chibuque, Jun Hyun Kim, Marcel Hohl, Christina Leslie, Jorge S. Reis-Filho, John H.J. Petrini
The MRE11 complex (comprising MRE11, RAD50, and NBS1) is integral to the maintenance of genome stability. We previously showed that a hypomorphic Mre11 mutant mouse strain (Mre11ATLD1/ATLD1) was highly susceptible to oncogene-induced breast cancer. Here we used a mammary organoid system to examine which MRE11-dependent responses are tumor-suppressive. We found that Mre11ATLD1/ATLD1 organoids exhibited
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Circadian de(regulation) in physiology: implications for disease and treatment Genes Dev. (IF 7.5) Pub Date : 2024-11-01 Leonardo Vinicius Monteiro de Assis, Achim Kramer
Time plays a crucial role in the regulation of physiological processes. Without a temporal control system, animals would be unprepared for cyclic environmental changes, negatively impacting their survival. Experimental studies have demonstrated the essential role of the circadian system in the temporal coordination of physiological processes. Translating these findings to humans has been challenging
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Notch induces transcription by stimulating release of paused RNA polymerase II Genes Dev. (IF 7.5) Pub Date : 2024-11-01 Julia M. Rogers, Claudia A. Mimoso, Benjamin J.E. Martin, Alexandre P. Martin, Jon C. Aster, Karen Adelman, Stephen C. Blacklow
Notch proteins undergo ligand-induced proteolysis to release a nuclear effector that influences a wide range of cellular processes by regulating transcription. Despite years of study, however, how Notch induces the transcription of its target genes remains unclear. Here, we comprehensively examine the response to human Notch1 across a time course of activation using high-resolution genomic assays of
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YY1 knockout in pro-B cells impairs lineage commitment, enabling unusual hematopoietic lineage plasticity Genes Dev. (IF 7.5) Pub Date : 2024-09-01 Sarmistha Banerjee, Sulagna Sanyal, Suchita Hodawadekar, Sarah Naiyer, Nasreen Bano, Anupam Banerjee, Joshua Rhoades, Dawei Dong, David Allman, Michael L. Atchison
During B-cell development, cells progress through multiple developmental stages, with the pro-B-cell stage defining commitment to the B-cell lineage. YY1 is a ubiquitous transcription factor that is capable of both activation and repression functions. We found here that knockout of YY1 at the pro-B-cell stage eliminates B lineage commitment. YY1 knockout pro-B cells can generate T lineage cells in
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NEAT1 promotes genome stability via m6A methylation-dependent regulation of CHD4 Genes Dev. (IF 7.5) Pub Date : 2024-09-01 Victoria Mamontova, Barbara Trifault, Anne-Sophie Gribling-Burrer, Patrick Bohn, Lea Boten, Pit Preckwinkel, Peter Gallant, Daniel Solvie, Carsten P. Ade, Dimitrios Papadopoulos, Martin Eilers, Tony Gutschner, Redmond P. Smyth, Kaspar Burger
Long noncoding (lnc)RNAs emerge as regulators of genome stability. The nuclear-enriched abundant transcript 1 (NEAT1) is overexpressed in many tumors and is responsive to genotoxic stress. However, the mechanism that links NEAT1 to DNA damage response (DDR) is unclear. Here, we investigate the expression, modification, localization, and structure of NEAT1 in response to DNA double-strand breaks (DSBs)
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Cancer neuroscience at the brain–body interface Genes Dev. (IF 7.5) Pub Date : 2024-09-01 Jeremy C. Borniger
Our approaches toward understanding cancer have evolved beyond cell-intrinsic and local microenvironmental changes within the tumor to encompass how the cancer interfaces with the entire host organism. The nervous system is uniquely situated at the interface between the brain and body, constantly receiving and sending signals back and forth to maintain homeostasis and respond to salient stimuli. It
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Temperature matters: the potential impact of thermoregulatory mechanisms in brain–body physiology Genes Dev. (IF 7.5) Pub Date : 2024-09-01 Elizabeth A. Repasky, Bonnie L. Hylander, Hemn Mohammadpour
Thermoregulation, responsible for maintaining a stable core temperature during wide fluctuations in external and internal thermal environments, is an iconic homeostatic process. However, we suggest that despite its fundamental physiological significance, the potential for required cool housing temperatures and thermoregulatory mechanisms to influence the interpretation of experimental data is not sufficiently
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The area postrema: a critical mediator of brain–body interactions Genes Dev. (IF 7.5) Pub Date : 2024-09-01 Daniëlle van de Lisdonk, Bo Li
The dorsal vagal complex contains three structures: the area postrema, the nucleus tractus solitarii, and the dorsal motor nucleus of the vagus. These structures are tightly linked, both anatomically and functionally, and have important yet distinct roles in not only conveying peripheral bodily signals to the rest of the brain but in the generation of behavioral and physiological responses. Reports
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Interoceptive inference and prediction in food-related disorders Genes Dev. (IF 7.5) Pub Date : 2024-09-01 Madhav Subramanian, Christoph A. Thaiss
The brain's capacity to predict and anticipate changes in internal and external environments is fundamental to initiating efficient adaptive responses, behaviors, and reflexes that minimize disruptions to physiology. In the context of feeding control, the brain predicts and anticipates responses to the consumption of dietary substances, thus driving adaptive behaviors in the form of food choices, physiological
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Decoding biology with massively parallel reporter assays and machine learning Genes Dev. (IF 7.5) Pub Date : 2024-09-01 Alyssa La Fleur, Yongsheng Shi, Georg Seelig
Massively parallel reporter assays (MPRAs) are powerful tools for quantifying the impacts of sequence variation on gene expression. Reading out molecular phenotypes with sequencing enables interrogating the impact of sequence variation beyond genome scale. Machine learning models integrate and codify information learned from MPRAs and enable generalization by predicting sequences outside the training
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Bridging brain and body in cancer Genes Dev. (IF 7.5) Pub Date : 2024-09-01 Michael Cross, Andrew Dillin, Thales Papagiannakopoulos
Recent work has highlighted the central role the brain–body axis plays in not only maintaining organismal homeostasis but also coordinating the body's response to immune and inflammatory insults. Here, we discuss how science is poised to address the many ways that our brain is directly involved with disease. In particular, we feel that combining cutting-edge tools in neuroscience with translationally
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What a wonderful world! Genes Dev. (IF 7.5) Pub Date : 2024-09-01 Claire Magnon
The world of cancer science is moving toward a paradigm shift in making connections with neuroscience. After decades of research on genetic instability and mutations or on the tumor microenvironment, emerging evidence suggests that a malignant tumor is able to hijack and use the brain and its network of peripheral and central neurons as disrupters of homeostasis in the body. Whole-body homeostasis
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Deciphering visceral instincts: a scientific quest to unravel food choices from molecules to mind Genes Dev. (IF 7.5) Pub Date : 2024-09-01 Emily Alway, Naama Reicher, Diego V. Bohórquez
The study of biological mechanisms, while crucial, cannot fully explain complex phenomena like the instinct to eat. The mind–body connection, as exemplified by the concept of “voodoo death,” highlights the profound influence of belief and cultural context on physiology. Indigenous knowledge systems further emphasize the interconnectedness of humans with their environment. Recent discoveries in gut–brain
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Consolidating roles of neuroimmune reflexes: specificity of afferent, central, and efferent signals in homeostatic immune networks Genes Dev. (IF 7.5) Pub Date : 2024-09-01 Kevin J. Tracey
Neural reflexes occupy a central role in physiological homeostasis. The vagus nerve is a major conduit for transmitting afferent and efferent signals in homeostatic reflex arcs between the body and the brain. Recent advances in neuroscience, immunology, and physiology have revealed important vagus nerve mechanisms in suppressing inflammation and treating rheumatoid arthritis and other autoimmune conditions
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Harnessing brain–body communication to understand cancer Genes Dev. (IF 7.5) Pub Date : 2024-09-01 Erica K. Sloan
Solid tumors that arise in the body interact with neurons, which influences cancer progression and treatment response. Here, we discuss key questions in the field, including defining the nature of interactions between tumors and neural circuits and defining how neural signals shape the tumor microenvironment. This information will allow us to optimally target neural signaling to improve outcomes for
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A germline PAF1 paralog complex ensures cell type-specific gene expression Genes Dev. (IF 7.5) Pub Date : 2024-09-01 Astrid Pold Vilstrup, Archica Gupta, Anna Jon Rasmussen, Anja Ebert, Sebastian Riedelbauch, Marie Vestergaard Lukassen, Rippei Hayashi, Peter Andersen
Animal germline development and fertility rely on paralogs of general transcription factors that recruit RNA polymerase II to ensure cell type-specific gene expression. It remains unclear whether gene expression processes downstream from such paralog-based transcription is distinct from that of canonical RNA polymerase II genes. In Drosophila, the testis-specific TBP-associated factors (tTAFs) activate
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A cellular identity crisis? Plasticity changes during aging and rejuvenation Genes Dev. (IF 7.5) Pub Date : 2024-09-01 Rebecca Gorelov, Konrad Hochedlinger
Cellular plasticity in adult multicellular organisms is a protective mechanism that allows certain tissues to regenerate in response to injury. Considering that aging involves exposure to repeated injuries over a lifetime, it is conceivable that cell identity itself is more malleable—and potentially erroneous—with age. In this review, we summarize and critically discuss the available evidence that
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Corrigendum: XBP-1 deficiency in the nervous system protects against amyotrophic lateral sclerosis by increasing autophagy Genes Dev. (IF 7.5) Pub Date : 2024-08-01 Claudio Hetz, Peter Thielen, Soledad Matus, Melissa Nassif, Felipe Court, Roberta Kiffin, Gabriela Martinez, Ana Maria Cuervo, Robert H. Brown, Laurie H. Glimcher
Genes & Development 23: 2294–2306 (2009)
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Corrigendum: TAp73 is a central transcriptional regulator of airway multiciliogenesis Genes Dev. (IF 7.5) Pub Date : 2024-08-01 Alice Nemajerova, Daniela Kramer, Saul S. Siller, Christian Herr, Orr Shomroni, Tonatiuh Pena, Cristina Gallinas Suazo, Katharina Glaser, Merit Wildung, Henrik Steffen, Anusha Sriraman, Fabian Oberle, Magdalena Wienken, Magali Hennion, Ramon Vidal, Bettina Royen, Mihai Alevra, Detlev Schild, Robert Bals, Jürgen Dönitz, Dietmar Riedel, Stefan Bonn, Ken-Ichi Takemaru, Ute M. Moll, Muriel Lizé
Genes & Development 30: 1300–1312 (2016)
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Developmental regulation of dermal adipose tissue by BCL11b Genes Dev. (IF 7.5) Pub Date : 2024-08-01 Sarah Traynor, Shashwati Bhattacharya, Kirill Batmanov, Lan Cheng, Angela Weller, Natalie Moore, Carmen Flesher, David Merrick
The distinct anatomic environment in which adipose tissues arise during organogenesis is a principle determinant of their adult expansion capacity. Metabolic disease results from a deficiency in hyperplastic adipose expansion within the dermal/subcutaneous depot; thus, understanding the embryonic origins of dermal adipose is imperative. Using single-cell transcriptomics throughout murine embryogenesis
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Heterozygous RPA2 variant as a novel genetic cause of telomere biology disorders Genes Dev. (IF 7.5) Pub Date : 2024-08-01 Rima Kochman, Ibrahima Ba, Maïlyn Yates, Vithura Pirabakaran, Florian Gourmelon, Dmitri Churikov, Marc Laffaille, Laëtitia Kermasson, Coline Hamelin, Isabelle Marois, Frédéric Jourquin, Laura Braud, Marianne Bechara, Elodie Lainey, Hilario Nunes, Philippe Breton, Morgane Penhouet, Pierre David, Vincent Géli, Christophe Lachaud, Alexandre Maréchal, Patrick Revy, Caroline Kannengiesser, Carole Saintomé
Premature telomere shortening or telomere instability is associated with a group of rare and heterogeneous diseases collectively known as telomere biology disorders (TBDs). Here we identified two unrelated individuals with clinical manifestations of TBDs and short telomeres associated with the identical monoallelic variant c.767A>G; Y256C in RPA2. Although the replication protein A2 (RPA2) mutant did
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TFEB controls expression of human syncytins during cell–cell fusion Genes Dev. (IF 7.5) Pub Date : 2024-08-01 Meagan N. Esbin, Liza Dahal, Vinson B. Fan, Joey McKenna, Eric Yin, Xavier Darzacq, Robert Tjian
During human development, a temporary organ is formed, the placenta, which invades the uterine wall to support nutrient, oxygen, and waste exchange between the mother and fetus until birth. Most of the human placenta is formed by a syncytial villous structure lined by syncytialized trophoblasts, a specialized cell type that forms via cell–cell fusion of underlying progenitor cells. Genetic and functional
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The MYC–MAF–SAGA axis drives oncogenic gene expression in multiple myeloma Genes Dev. (IF 7.5) Pub Date : 2024-08-01 Hongkuan Wang, Hong Wen, Xiaobing Shi
The SAGA complex is an evolutionarily conserved histone acetyltransferase complex and transcription coactivator essential for development and disease. Dysregulation of SAGA is implicated in various human diseases, including cancer. In this issue of Genes & Development, Chen et al. (doi:10.1101/gad.351789.124) uncover a critical role for SAGA in multiple myeloma wherein SAGA's ADA2B component is required
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The SAGA acetyltransferase module is required for the maintenance of MAF and MYC oncogenic gene expression programs in multiple myeloma Genes Dev. (IF 7.5) Pub Date : 2024-08-01 Ying-Jiun C. Chen, Govinal Badiger Bhaskara, Yue Lu, Kevin Lin, Sharon Y.R. Dent
Despite recent advances in therapeutic treatments, multiple myeloma (MM) remains an incurable malignancy. Epigenetic factors contribute to the initiation, progression, relapse, and clonal heterogeneity in MM, but our knowledge on epigenetic mechanisms underlying MM development is far from complete. The SAGA complex serves as a coactivator in transcription and catalyzes acetylation and deubiquitylation
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An old dog with new tricks: TFEB promotes syncytin expression and cell fusion in the human placenta Genes Dev. (IF 7.5) Pub Date : 2024-08-01 Stephen J. Renaud
In the human placenta, cell fusion is crucial for forming the syncytiotrophoblast, a multinucleated giant cell essential for maintaining pregnancy and ensuring fetal health. The formation of the syncytiotrophoblast is catalyzed by the evolutionarily modern fusogens syncytin-1 and syncytin-2. In this issue of Genes & Development, Esbin and colleagues (doi:10.1101/gad.351633.124) reveal a critical role
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Therapeutic targeting of RNA for neurological and neuromuscular disease Genes Dev. (IF 7.5) Pub Date : 2024-08-01 Jodi. L. Bubenik, Marina M. Scotti, Maurice S. Swanson
Neurological and neuromuscular diseases resulting from familial, sporadic, or de novo mutations have devasting personal, familial, and societal impacts. As the initial product of DNA transcription, RNA transcripts and their associated ribonucleoprotein complexes provide attractive targets for modulation by increasing wild-type or blocking mutant allele expression, thus relieving downstream pathological
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Corrigendum: Members of the heat-shock protein 70 family promote cancer cell growth by distinct mechanisms Genes Dev. (IF 7.5) Pub Date : 2024-07-01 Mikkel Rohde, Mads Daugaard, Mette Hartvig Jensen, Kristian Helin, Jesper Nylandsted, Marja Jäättelä
Genes & Development 19: 570–582 (2005)
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Hyd/UBR5 defines a tumor suppressor pathway that links Polycomb repressive complex to regulated protein degradation in tissue growth control and tumorigenesis Genes Dev. (IF 7.5) Pub Date : 2024-07-01 Pei Wen, Huiyan Lei, Hua Deng, Su Deng, Carla Rodriguez Tirado, Meiling Wang, Ping Mu, Yonggang Zheng, Duojia Pan
Tumor suppressor genes play critical roles in normal tissue homeostasis, and their dysregulation underlies human diseases including cancer. Besides human genetics, model organisms such as Drosophila have been instrumental in discovering tumor suppressor pathways that were subsequently shown to be highly relevant in human cancer. Here we show that hyperplastic disc (Hyd), one of the first tumor suppressors