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An Overview on the Complexity of OCT4: at the Level of DNA, RNA and Protein

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Abstract

OCT4 plays critical roles in self-renewal and pluripotency maintenance of embryonic stem cells, and is considered as one of the main stemness markers. It also has pivotal roles in early stages of embryonic development. Most studies on OCT4 have focused on the expression and function of OCT4A, which is the biggest isoform of OCT4 known so far. Recently, many studies have shown that OCT4 has various transcript variants, protein isoforms, as well as pseudogenes. Distinguishing the expression and function of these variants and isoforms is a big challenge in expression profiling studies of OCT4. Understanding how OCT4 is functioning in different contexts, depends on knowing of where and when each of OCT4 transcripts, isoforms and pseudogenes are expressed. Here, we review OCT4 known transcripts, isoforms and pseudogenes, as well as its interactions with other proteins, and emphasize the importance of discriminating each of them in order to understand the exact function of OCT4 in stem cells, normal development and development of diseases.

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Abbreviations

Arid3a:

AT-rich interactive domain-containing protein 3A

Asf1a:

Anti-Silencing Function 1A

BLAST:

Basic local alignment search tool

c-MYC:

Cellular-Myelocytomatosis

CTD:

N-transactivation domain

ChIP:

Chromatin Immunopercipitation

Cdy1:

Chromodomain Y-Linked 1

DNA:

Deoxyribonucleic acid

Dppa5:

Developmental Pluripotency Associated 5

Dnmt3b:

DNA-methyltransferase 3 beta

Dax1:

Dosage-sensitive sex reversal

Dpf2:

Double PHD Fingers 2

ESC:

Embryonic stem cell

ESRRB:

Estrogen Related Receptor Beta

Fbxo15:

F-Box Protein 15

HTMase:

Histone demethylase

H3K9me3:

Histon 3 Lysine 9 three methylation

HCC:

Hepatocellular carcinoma

Hells:

Helicase, Lymphoid Specific

Hdac1:

Histone deacetylase 1

IRES:

Internal ribosome entry site

KLF4:

Kruppel-like factor 4

Lefty1:

Left-Right Determination Factor 1

Lig3:

DNA NA Ligase 3

LSD1:

Lysine-specific histone demethylase 1

Msh2:

MutS homolog 2

MTA1:

Metastasis-associated protein 1

NTD:

N-transactivation domain

Nac1:

Nucleus accumbens-associated protein 1

NurD:

Ncleosome remodeling and deacetylase

OCT4:

Octamer transcription factor 4

Otx2:

Orthodenticle Homeobox 2

Pit-1a:

Pituitary-specific positive transcription factor 1

pg:

Pseudogene

Phc1:

Polyhomeotic-like protein 1

Pnkp:

Polynucleotide Kinase 3’-Phosphatase

Prkdc:

Protein Kinase

DNA:

Activated, Catalytic Subunit

PTMs:

Post translational modifications

PGCs:

Primordial Germ Cells

RNA:

Ribonucleic acid

RA:

Retinoic acid

NT-2:

NTERA-2

RT-qPCR:

Reverse transcription-quantitative Polymerase Chain Reaction

RPA1:

Replication protein A1

Rbbp7:

RB Binding Protein 7

Rcor2:

REST Corepressor 2

SOX2:

SRY-box transcription factor 2

SNP:

Single nucleotide polymorphism

SINE:

Short interespersed nuclear repetitive DNA element

Spp1:

Secreted Phosphoprotein 1;

Sall1:

Spalt Like Transcription Factor 1

Sp1:

Specificity protein 1

SWI/SNF:

SWItch/Sucrose Non-Fermentable

Sf1:

Splicing factor 1

TSS:

Transcription start site

TF:

Transcription factor

TE:

Transposable element

Tcfcp2l1:

Transcription Factor CP2 Like 1

TGF-b:

Transforming growth factor beta

UCSC:

University of California Santa Cruz

UTF1:

Undifferentiated Embryonic Cell Transcription Factor 1

Up1:

Uridine Phosphorylase 1

VSELs:

Very small embryonic-like stem cells

WT1:

Wilm’s tumor 1

MEF-2:

Myocyte enhancer factor-2

Wnt:

Wingless-related integration site

Xrcc1:

X-ray repair cross-complementing protein 1

yy1:

Yin Yang 1

Zfp:

Zinc finger protein

Zfp15:

Zinc finger protein 15

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Authors and Affiliations

  1. Department of Anatomy and Developmental Biology, Development and Stem Cells Program, Biomedicine Discovery Institute, Monash University, Melbourne, Australia

    Majid Mehravar

  2. Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran

    Fatemeh Ghaemimanesh

  3. Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Ensieh M. Poursani

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  1. Majid Mehravar
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  2. Fatemeh Ghaemimanesh
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  3. Ensieh M. Poursani
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M.M. and E.M.P. designed and wrote the manuscript. F.G. edited the manuscript.

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Mehravar, M., Ghaemimanesh, F. & Poursani, E.M. An Overview on the Complexity of OCT4: at the Level of DNA, RNA and Protein. Stem Cell Rev and Rep 17, 1121–1136 (2021). https://doi.org/10.1007/s12015-020-10098-3

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