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Caltech

General Biology Seminar

Tuesday, November 15, 2011
4:00pm to 5:00pm
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Kerckhoff 119
Dynamics of the epigenetic landscape during mouse hematopoietic differentiation
Ross Hardison, professor of biochemistry and molecular biology, the Pennsylvania State University,
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. 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. Current studies extend these analyses to the sister cell lineage, megakaryocytes, and earlier bipotential progenitors.
For more information, please contact Julia Boucher by phone at 4952 or by email at [email protected].