Title

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

UMMS Affiliation

Program in Systems Biology; Department of Biochemistry and Molecular Pharmacology

Publication Date

2019-08-30

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Cancer Biology | Cell Biology | Genetic Phenomena | Genetics and Genomics | Molecular Biology | Structural Biology | Systems Biology

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.

Keywords

Cohesin, Stag1, Stag2, chromatin, hematopoietic stem cells, mouse models, myelodysplasia, nuclear topology

DOI of Published Version

10.1016/j.stem.2019.08.003

Source

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

Journal/Book/Conference Title

Cell stem cell

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

31495782

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