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Dynamics of the epigenetic landscape during erythroid differentiation after GATA1 restoration

2011; Cold Spring Harbor Laboratory Press; Volume: 21; Issue: 10 Linguagem: Inglês

10.1101/gr.125088.111

1549-5469

Wei-Sheng Wu, Yong Cheng, Cheryl A. Keller, Jason Ernst, Swathi A. Kumar, Tejaswini Mishra, Christapher S. Morrissey, Christine M. Dorman, Kuan-Bei Chen, Daniela I. Drautz, Belinda Giardine, Yoichiro Shibata, Lingyun Song, Max Pimkin, Gregory E. Crawford, Terrence S. Furey, Manolis Kellis, Webb Miller, James Taylor, Stephan C. Schuster, Yu Zhang, Francesca Chiaromonte, Gerd A. Blobel, Mitchell J. Weiss, Ross C. Hardison,

RNA modifications and cancer

Interplays among lineage-specific nuclear proteins, chromatin modifying enzymes, and the basal transcription machinery govern cellular differentiation, but their dynamics of action and coordination with transcriptional control are not fully understood. Alterations in chromatin structure appear to establish a permissive state for gene activation at some loci, but they play an integral role in activation at other loci. To determine the predominant roles of chromatin states and factor occupancy in directing gene regulation during differentiation, we mapped chromatin accessibility, histone modifications, and nuclear factor occupancy genome-wide during mouse erythroid differentiation dependent on the master regulatory transcription factor GATA1. Notably, despite extensive changes in gene expression, the chromatin state profiles (proportions of a gene in a chromatin state dominated by activating or repressive histone modifications) and accessibility remain largely unchanged during GATA1-induced erythroid differentiation. In contrast, gene induction and repression are strongly associated with changes in patterns of transcription factor occupancy. Our results indicate that during erythroid differentiation, the broad features of chromatin states are established at the stage of lineage commitment, largely independently of GATA1. These determine permissiveness for expression, with subsequent induction or repression mediated by distinctive combinations of transcription factors.