GSE30142
Genome-wide maps of epigenetic features in G1E model and in mouse primary erythroblasts.
Interplays among lineage specific nuclear proteins, chromatin modifying enzymes and the basal transcription machinery govern cellular differentiation, but their dynamics of actions 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. Remarkably, 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. Overall design: Using ChIP-Seq technology to examine DNase hypersensitivity, three transcription factors, and four histone modifications in Gata1-null murine G1E line and rescued G1E-ER4 subline, and also two of the transcription factors in mouse primary erythroblasts. ChIP input DNA was sequenced in each cell type as controls.