Smarcc1/Baf155 couples self-renewal gene repression with changes in chromatin structure in mouse embryonic stem cells

Schaniel, C., Ang, Y. S., Ratnakumar, K., Cormier, C., James, T., Bernstein, E., Lemischka, I. R., Paddison, P. J. (2009) Smarcc1/Baf155 couples self-renewal gene repression with changes in chromatin structure in mouse embryonic stem cells. Stem Cells, 27 (12). pp. 2979-2991.

URL: http://www.ncbi.nlm.nih.gov/pubmed/19785031
DOI: 10.1002/stem.223

Abstract

Little is known about the molecular mechanism(s) governing differentiation decisions in embryonic stem cells (ESCs). To identify factors critical for ESC lineage formation, we carried out a functional genetic screen for factors affecting Nanog promoter activity during mESC differentiation. We report that members of the PBAF chromatin remodeling complex, including Smarca4/Brg1, Smarcb1/ Baf47, Smarcc1/Baf155, and Smarce1/Baf57, are required for the repression of Nanog and other self-renewal gene expression upon mouse ESC (mESC) differentiation. Knockdown of Smarcc1 or Smarce1 suppressed loss of Nanog expression in multiple forms of differentiation. This effect occurred in the absence of self-renewal factors normally required for Nanog expression (e.g., Oct4), possibly indicating that changes in chromatin structure, rather than loss of self-renewal gene transcription per se, trigger differentiation. Consistent with this notion, mechanistic studies demonstrated that expression of Smarcc1 is necessary for heterochromatin formation and chromatin compaction during differentiation. Collectively, our data reveal that Smarcc1 plays important roles in facilitating mESCs differentiation by coupling gene repression with global and local changes in chromatin structure. © AlphaMed Press.

Item Type: Paper
Uncontrolled Keywords: Differentiation ESC Functional genetics Nanog RNAi Smarcc1
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > Chromatin dynamics
organism description > animal > mammal > rodent > mouse
therapies > stem cells
CSHL Authors:
Communities: CSHL labs > Paddison lab
Depositing User: Matt Covey
Date Deposited: 19 Feb 2013 16:45
Last Modified: 19 Feb 2013 16:45
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27455

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