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
Related Resources
PubMed ID
31495782
Repository Citation
Viny AD, Liu Y, Dekker J, Levine RL. (2019). Cohesin Members Stag1 and Stag2 Display Distinct Roles in Chromatin Accessibility and Topological Control of HSC Self-Renewal and Differentiation. Program in Systems Biology Publications. https://doi.org/10.1016/j.stem.2019.08.003. Retrieved from https://escholarship.umassmed.edu/sysbio_pubs/157
Comments
Full author list omitted for brevity. For the full list of authors, see article.