Ezh2 Orchestrates Gene Expression for the Stepwise Differentiation of Tissue-Specific Stem Cells

Ezhkova, E., Pasolli, H. A., Parker, J. S., Stokes, N., Su, I. H., Hannon, G. J., Tarakhovsky, A., Fuchs, E. (2009) Ezh2 Orchestrates Gene Expression for the Stepwise Differentiation of Tissue-Specific Stem Cells. Cell, 136 (6). pp. 1122-1135. ISSN 0092-8674

URL: http://www.ncbi.nlm.nih.gov/pubmed/19303854
DOI: 10.1016/j.cell.2008.12.043

Abstract

Although in vitro studies of embryonic stem cells have identified polycomb repressor complexes (PRCs) as key regulators of differentiation, it remains unclear as to how PRC-mediated mechanisms control fates of multipotent progenitors in developing tissues. Here, we show that an essential PRC component, Ezh2, is expressed in epidermal progenitors but diminishes concomitant with embryonic differentiation and with postnatal decline in proliferative activity. We show that Ezh2 controls proliferative potential of basal progenitors by repressing the Ink4A-Ink4B locus and tempers the developmental rate of differentiation by preventing premature recruitment of AP1 transcriptional activator to the structural genes that are required for epidermal differentiation. Together, our studies reveal that PRCs control epigenetic modifications temporally and spatially in tissue-restricted stem cells. They maintain their proliferative potential and globally repressing undesirable differentiation programs while selectively establishing a specific terminal differentiation program in a stepwise fashion.

Item Type: Paper
Uncontrolled Keywords: POLYCOMB GROUP PROTEINS SELF-RENEWAL DEVELOPMENTAL REGULATORS CORNIFIED ENVELOPE PROXIMAL PROMOTER BMI-1 SKIN METHYLATION CHROMATIN BARRIER SIGNALING DNA
Subjects: bioinformatics
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 > epigenetics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > epigenetics

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
therapies > stem cells
CSHL Authors:
Communities: CSHL labs > Hannon lab
Depositing User: Matt Covey
Date Deposited: 21 Feb 2013 16:44
Last Modified: 21 Feb 2013 16:44
PMCID: PMC2716120
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27375

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