美国纽约纪念斯隆·凯特琳癌症中心Ross L. Levine研究小组的一项最新研究发现，cohesin蛋白成员Stag1和Stag2在血液干细胞（HSC）自我更新和分化的染色质可及性和拓扑控制方面发挥着不同的作用。该研究2019年9月5日在线发表于《细胞—干细胞》。

研究人员发现造血干细胞和祖细胞（HSPC）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结合一组共同的基因组位点，Stag2结合位点的组分即使在Stag2缺陷的HSPC中也未被Stag1所占据。尽管Stag2和Stag1的同时丢失阻碍了造血功能，但单独的Stag2缺失降低了染色质可及性和谱系经典基因（包括Ebf1和Pax5）的转录，导致自我更新增加和HSPC向B细胞谱系分化的减少。这些数据说明Stag2在转化和转录失调中的作用不同于它在染色体分离中与Stag1的共有角色。

据悉，转录调节因子，包括cohesin复合物成员STAG2，在癌症中反复发生突变。STAG2在基因调控、血液生成和肿瘤抑制中的作用仍未得到解决。

附：英文原文

Title: Cohesin Members Stag1 and Stag2 Display Distinct Roles in Chromatin Accessibility and Topological Control of HSC Self-Renewal and Differentiation

Author: Aaron D. Viny, Robert L. Bowman, Yu Liu, Vincent-Philippe Lavallée, Shira E. Eisman, Wenbin Xiao, Benjamin H. Durham, Anastasia Navitski, Jane Park, Stephanie Braunstein, Besmira Alija, Abdul Karzai, Isabelle S. Csete, Matthew Witkin, Elham Azizi, Timour Baslan, Christopher J. Ott, Dana Pe’er, Job Dekker, Richard Koche, Ross L. Levine

Issue&Volume: 5 September 2019

Abstract: 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.

DOI: 10.1016/j.stem.2019.08.003

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30338-8