NuRD suppresses pluripotency gene expression to promote transcriptional heterogeneity and lineage commitment
| Autor: | Kentaro Nakagawa, Peter Humphreys, Antony Hynes-Allen, Aoife O'Shaughnessy, Jason Signolet, Ita Costello, Paul Bertone, Donna Leaford, Paulina A. Latos, Tuezer Kalkan, Brian Hendrich, Philip Brennecke, John Strouboulis, William Mansfield, Nicola Reynolds, Axel Behrens, Olukunbi Mosaku, Remco Loos |
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| Přispěvatelé: | Bertone, Paul [0000-0001-5059-4829], Hendrich, Brian [0000-0002-0231-3073], Apollo - University of Cambridge Repository |
| Rok vydání: | 2012 |
| Předmět: |
Pluripotent Stem Cells
Cellular differentiation Population Biology Article Chromatin remodeling Genetic Heterogeneity Mice 03 medical and health sciences 0302 clinical medicine Genetics Animals Cell Lineage Induced pluripotent stem cell education Transcription factor Cells Cultured Embryonic Stem Cells 030304 developmental biology Mice Knockout Regulation of gene expression 0303 health sciences education.field_of_study Gene Expression Regulation Developmental Cell Differentiation Cell Biology Mi-2/NuRD complex Embryonic stem cell DNA-Binding Proteins Molecular Medicine 030217 neurology & neurosurgery Mi-2 Nucleosome Remodeling and Deacetylase Complex Transcription Factors |
| Zdroj: | Reynolds, N, Latos, P, Hynes-Allen, A, Loos, R, Leaford, D, O'Shaughnessy, A, Mosaku, O, Signolet, J, Brennecke, P, Kalkan, T, Costello, I, Humphreys, P, Mansfield, W, Nakagawa, K, Strouboulis, J, Behrens, A, Bertone, P & Hendrich, B 2012, ' NuRD Suppresses Pluripotency Gene Expression to Promote Transcriptional Heterogeneity and Lineage Commitment ', Cell Stem Cell, vol. 10, no. 5, pp. 583-594 . https://doi.org/10.1016/j.stem.2012.02.020 Cell Stem Cell |
| DOI: | 10.1016/j.stem.2012.02.020 |
| Popis: | Summary 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. Graphical Abstract Highlights ► NuRD directly regulates the transcription of pluripotency genes ► The repressive activity of NuRD is required for ESC differentiation ► NuRD mediates transcriptional heterogeneity in ESC populations ► Transcription levels are determined by balanced activation and silencing |
| Databáze: | OpenAIRE |
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