当前位置：
X-MOL 学术
›
Cell Stem Cell
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Cohesin Members Stag1 and Stag2 Display Distinct Roles in Chromatin Accessibility and Topological Control of HSC Self-Renewal and Differentiation.
Cell Stem Cell ( IF 19.8 ) Pub Date : 2019-09-05 , DOI: 10.1016/j.stem.2019.08.003 Aaron D Viny 1 , Robert L Bowman 2 , Yu Liu 3 , Vincent-Philippe Lavallée 4 , Shira E Eisman 2 , Wenbin Xiao 5 , Benjamin H Durham 5 , Anastasia Navitski 2 , Jane Park 6 , Stephanie Braunstein 2 , Besmira Alija 2 , Abdul Karzai 2 , Isabelle S Csete 2 , Matthew Witkin 6 , Elham Azizi 4 , Timour Baslan 7 , Christopher J Ott 8 , Dana Pe'er 4 , Job Dekker 9 , Richard Koche 6 , Ross L Levine 1
Cell Stem Cell ( IF 19.8 ) Pub Date : 2019-09-05 , DOI: 10.1016/j.stem.2019.08.003 Aaron D Viny 1 , Robert L Bowman 2 , Yu Liu 3 , Vincent-Philippe Lavallée 4 , Shira E Eisman 2 , Wenbin Xiao 5 , Benjamin H Durham 5 , Anastasia Navitski 2 , Jane Park 6 , Stephanie Braunstein 2 , Besmira Alija 2 , Abdul Karzai 2 , Isabelle S Csete 2 , Matthew Witkin 6 , Elham Azizi 4 , Timour Baslan 7 , Christopher J Ott 8 , Dana Pe'er 4 , Job Dekker 9 , Richard Koche 6 , Ross L Levine 1
Affiliation
|
Transcriptional regulators, including the cohesin complex member STAG2, are recurrently mutated in cancer. The role of STAG2 in gene regulation, hematopoiesis, and tumor suppression remains unresolved. We show that Stag2 deletion in hematopoietic stem and progenitor cells (HSPCs) results in altered hematopoietic function, increased self-renewal, and impaired differentiation. Chromatin immunoprecipitation (ChIP) sequencing revealed that, although Stag2 and Stag1 bind a shared set of genomic loci, a component of Stag2 binding sites is unoccupied by Stag1, even in Stag2-deficient HSPCs. Although concurrent loss of Stag2 and Stag1 abrogated hematopoiesis, Stag2 loss alone decreased chromatin accessibility and transcription of lineage-specification genes, including Ebf1 and Pax5, leading to increased self-renewal and reduced HSPC commitment to the B cell lineage. Our data illustrate a role for Stag2 in transformation and transcriptional dysregulation distinct from its shared role with Stag1 in chromosomal segregation.
中文翻译：
粘附素成员Stag1和Stag2在染色质可及性和HSC自我更新和分化的拓扑控制中显示不同的作用。
在癌症中，包括黏附蛋白复合物成员STAG2在内的转录调节因子经常发生突变。STAG2在基因调节，造血和肿瘤抑制中的作用仍未解决。我们显示，造血干细胞和祖细胞（HSPCs）中的Stag2缺失导致造血功能改变，自我更新增加和分化受损。染色质免疫沉淀（ChIP）测序显示，尽管Stag2和Stag1结合了一组共享的基因组位点，但即使在Stag2缺失的HSPC中，Stag1也不占据Stag2结合位点的组成部分。尽管同时丢失Stag2和Stag1废除了造血功能，但仅Stag2丢失会降低染色质可及性和谱系特异性基因（包括Ebf1和Pax5）的转录，导致自我更新增加，HSPC对B细胞谱系的投入减少。我们的数据说明了Stag2在转化和转录失调中的作用，与Stag1在染色体分离中的共同作用不同。
更新日期：2019-11-09
中文翻译：
粘附素成员Stag1和Stag2在染色质可及性和HSC自我更新和分化的拓扑控制中显示不同的作用。
在癌症中，包括黏附蛋白复合物成员STAG2在内的转录调节因子经常发生突变。STAG2在基因调节，造血和肿瘤抑制中的作用仍未解决。我们显示，造血干细胞和祖细胞（HSPCs）中的Stag2缺失导致造血功能改变，自我更新增加和分化受损。染色质免疫沉淀（ChIP）测序显示，尽管Stag2和Stag1结合了一组共享的基因组位点，但即使在Stag2缺失的HSPC中，Stag1也不占据Stag2结合位点的组成部分。尽管同时丢失Stag2和Stag1废除了造血功能，但仅Stag2丢失会降低染色质可及性和谱系特异性基因（包括Ebf1和Pax5）的转录，导致自我更新增加，HSPC对B细胞谱系的投入减少。我们的数据说明了Stag2在转化和转录失调中的作用，与Stag1在染色体分离中的共同作用不同。
京公网安备 11010802027423号