Key regulatory genes, suppressed by Polycomb and H3K27me3, become active during normal differentiation and induced reprogramming. Using the wellcharacterized enhancer/promoter pair of MYOD1 as a model, we have identified a critical role for enhancers in reprogramming. We observed an unexpected nucleosome-depleted region (NDR) at the H3K4me1-enriched enhancer at which transcriptional regulators initially bind, leading to subsequent changes in the chromatin at the cognate promoter. Exogenous Myod1 activates its own transcription by binding first at the enhancer, leading to an NDR and transcription-permissive chromatin at the associated MYOD1 promoter. Exogenous OCT4 also binds first to the permissive MYOD1 enhancer but has a different effect on the cognate promoter, where the monovalent H3K27me3 marks are converted to the bivalent state characteristic of stem cells. Genome-wide, a high percentage of Polycomb targets are associated with putative enhancers in permissive states, suggesting that they may provide a widespread avenue for the initiation of cell-fate reprogramming.

Item Type:	Refereed Article
Keywords:	DNA methylation, nucleosome positions, histone modifications, cell reprogramming
Research Division:	Biological Sciences
Research Group:	Genetics
Research Field:	Epigenetics (incl. genome methylation and epigenomics)
Objective Division:	Expanding Knowledge
Objective Group:	Expanding knowledge
Objective Field:	Expanding knowledge in the biological sciences
UTAS Author:	Taberlay, PC (Associate Professor Phillippa Taberlay)
ID Code:	101256
Year Published:	2011
Web of Science® Times Cited:	137
Deposited By:	Medicine
Deposited On:	2015-06-15
Last Modified:	2017-11-02
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