| Literature DB >> 31495782 |
Aaron D Viny1, Robert L Bowman2, Yu Liu3, Vincent-Philippe Lavallée4, Shira E Eisman2, Wenbin Xiao5, Benjamin H Durham5, Anastasia Navitski2, Jane Park6, Stephanie Braunstein2, Besmira Alija2, Abdul Karzai2, Isabelle S Csete2, Matthew Witkin6, Elham Azizi4, Timour Baslan7, Christopher J Ott8, Dana Pe'er4, Job Dekker9, Richard Koche6, Ross L Levine10.
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.Entities:
Keywords: Cohesin; Stag1; Stag2; chromatin; hematopoietic stem cells; mouse models; myelodysplasia; nuclear topology
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Year: 2019 PMID： 31495782 PMCID： PMC6842438 DOI： 10.1016/j.stem.2019.08.003
Source DB: PubMed Journal: Cell Stem Cell ISSN： 1875-9777 Impact factor: 24.633