title: Polycomb-repressed genes have permissive enhancers that initiate reprogramming.
abstract: Key regulatory genes, suppressed by Polycomb and H3K27me3, become active during normal differentiation and induced reprogramming. Using the well-characterized 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.
authors.affiliation: Department of Urology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Phillippa C
authors.initials: PC
authors.lastname: Taberlay
authors.forename: Theresa K
authors.initials: TK
authors.lastname: Kelly
authors.forename: Chun-Chi
authors.initials: CC
authors.lastname: Liu
authors.forename: Jueng Soo
authors.initials: JS
authors.lastname: You
authors.forename: Daniel D
authors.initials: DD
authors.lastname: De Carvalho
authors.forename: Tina B
authors.initials: TB
authors.lastname: Miranda
authors.forename: Xianghong J
authors.initials: XJ
authors.lastname: Zhou
authors.forename: Gangning
authors.initials: G
authors.lastname: Liang
authors.forename: Peter A
authors.initials: PA
authors.lastname: Jones
mesh_terms: D000818:Animals; D002460:Cell Line; D004742:Enhancer Elements, Genetic; D057890:Epigenomics; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D051379:Mice; D017570:MyoD Protein / Q000235:genetics; D009707:Nucleosomes / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D063146:Polycomb-Group Proteins; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000378:metabolism*
chemical_list: D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D009707:Nucleosomes; D050814:Octamer Transcription Factor-3; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins