Chromatin modifiers and remodellers: regulators of cellular differentiation
Taiping Chen,Sharon Y.R. Dent +1 more
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TLDR
Genome-wide profiling of pluripotent cells and differentiated cells suggests global chromatin remodelling during differentiation, which results in a progressive transition from a fairly open chromatin configuration to a more compact state, rather than merely stabilizing the gene expression changes that are driven by developmental transcription factors.Abstract:
This Review describes the diverse roles for histone-modifying and chromatin-remodelling enzymes in mammalian differentiation. These enzymes are involved in both maintaining pluripotency and specifying cell lineage commitment. Recent progress includes their functional characterization in mouse modelsin vivoand a new appreciation of their multifaceted molecular functions. Cellular differentiation is, by definition, epigenetic. Genome-wide profiling of pluripotent cells and differentiated cells suggests global chromatin remodelling during differentiation, which results in a progressive transition from a fairly open chromatin configuration to a more compact state. Genetic studies in mouse models show major roles for a variety of histone modifiers and chromatin remodellers in key developmental transitions, such as the segregation of embryonic and extra-embryonic lineages in blastocyst stage embryos, the formation of the three germ layers during gastrulation and the differentiation of adult stem cells. Furthermore, rather than merely stabilizing the gene expression changes that are driven by developmental transcription factors, there is emerging evidence that chromatin regulators have multifaceted roles in cell fate decisions.read more
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References
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TL;DR: The first genome-wide, single-base-resolution maps of methylated cytosines in a mammalian genome, from both human embryonic stem cells and fetal fibroblasts, along with comparative analysis of messenger RNA and small RNA components of the transcriptome, several histone modifications, and sites of DNA-protein interaction for several key regulatory factors were presented in this article.
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Histone H3K27ac separates active from poised enhancers and predicts developmental state
Menno P. Creyghton,Albert W. Cheng,G. Grant Welstead,Tristan Kooistra,Bryce W. Carey,Eveline J. Steine,Jacob H. Hanna,Michael A. Lodato,Garrett M. Frampton,Phillip A. Sharp,Laurie A. Boyer,Richard A. Young,Rudolf Jaenisch +12 more
TL;DR: The epigenetic landscape of enhancer elements in embryonic stem cells and several adult tissues in the mouse is interrogated and it is found that histone H3K27ac distinguishes active enhancers from inactive/poised enhancers and poised enhancer networks provide clues to unrealized developmental programs.
Journal ArticleDOI
Formation of Pluripotent Stem Cells in the Mammalian Embryo Depends on the POU Transcription Factor Oct4
Jennifer Nichols,Branko Zevnik,Konstantinos Anastassiadis,Hitoshi Niwa,Daniela Klewe-Nebenius,Ian Chambers,Hans R. Schöler,Austin Smith +7 more
TL;DR: It is reported that the activity of Oct4 is essential for the identity of the pluripotential founder cell population in the mammalian embryo and also determines paracrine growth factor signaling from stem cells to the trophectoderm.