Dynamics of the epigenetic landscape during erythroid differentiation after GATA1 restoration
- Weisheng Wu1,
- Yong Cheng1,
- Cheryl A. Keller1,
- Jason Ernst2,
- Swathi Ashok Kumar1,
- Tejaswini Mishra1,
- Christapher Morrissey1,
- Christine M. Dorman1,
- Kuan-Bei Chen1,
- Daniela Drautz1,
- Belinda Giardine1,
- Yoichiro Shibata3,
- Lingyun Song3,
- Maxim Pimkin4,
- Gregory E. Crawford3,
- Terrence S. Furey5,
- Manolis Kellis2,
- Webb Miller1,
- James Taylor6,
- Stephan C. Schuster1,
- Yu Zhang1,
- Francesca Chiaromonte1,
- Gerd A. Blobel4,
- Mitchell J. Weiss4 and
- Ross C. Hardison1,7
- 1 Pennsylvania State University;
- 2 Massachusetts Institute of Technology;
- 3 Duke University;
- 4 Children's Hospital of Philadelphia;
- 5 University of North Carolina - Chapel Hill;
- 6 Emory University
- ↵* Corresponding author; email: rch8{at}psu.edu
Abstract
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.
- Received April 21, 2011.
- Accepted July 11, 2011.
- Copyright © 2011, Cold Spring Harbor Laboratory Press
This manuscript is Open Access.
