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Publication : NuRD suppresses pluripotency gene expression to promote transcriptional heterogeneity and lineage commitment.

First Author  Reynolds N Year  2012
Journal  Cell Stem Cell Volume  10
Issue  5 Pages  583-94
PubMed ID  22560079 Mgi Jnum  J:319679
Mgi Id  MGI:6205368 Doi  10.1016/j.stem.2012.02.020
Citation  Reynolds N, et al. (2012) NuRD suppresses pluripotency gene expression to promote transcriptional heterogeneity and lineage commitment. Cell Stem Cell 10(5):583-94
abstractText  Transcriptional heterogeneity within embryonic stem cell (ESC) populations has been suggested as a mechanism by which a seemingly homogeneous cell population can initiate differentiation into an array of different cell types. Chromatin remodeling proteins have been shown to control transcriptional variability in yeast and to be important for mammalian ESC lineage commitment. Here we show that the Nucleosome Remodeling and Deacetylation (NuRD) complex, which is required for ESC lineage commitment, modulates both transcriptional heterogeneity and the dynamic range of a set of pluripotency genes in ESCs. In self-renewing conditions, the influence of NuRD at these genes is balanced by the opposing action of self-renewal factors. Upon loss of self-renewal factors, the action of NuRD is sufficient to silence transcription of these pluripotency genes, allowing cells to exit self-renewal. We propose that modulation of transcription levels by NuRD is key to maintaining the differentiation responsiveness of pluripotent cells.
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