Cohesin Members Stag1 and Stag2 Display Distinct Roles in Chromatin Accessibility and Topological Control of HSC Self-Renewal and Differentiation
UMass Chan AffiliationsDepartment of Biochemistry and Molecular Pharmacology
Program in Systems Biology
Document TypeJournal Article
hematopoietic stem cells
Amino Acids, Peptides, and Proteins
Genetics and Genomics
MetadataShow full item record
AbstractTranscriptional 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.
Cell Stem Cell. 2019 Aug 30. pii: S1934-5909(19)30338-8. doi: 10.1016/j.stem.2019.08.003. [Epub ahead of print] Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/49886
Full author list omitted for brevity. For the full list of authors, see article.
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