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Learn MoreGene network transitions in embryos and fate-changing contexts involve combinations of transcription factors. A subset of fate-changing transcription factors act as pioneers; they scan and target nucleosomal DNA and initiate cooperative events that can open the local chromatin. But a gap has remained in understanding how molecular interactions with the nucleosome, beyond interactions with the DNA helix, contribute to the chromatin opening phenomenon. Here we identified a short alpha-helical region, conserved among FoxA pioneer factors and separated from the DNA binding domain, that interacts with core histones and is necessary for chromatin opening in vitro. The same domain is necessary for chromatin opening in early mouse embryos and for normal embryonic development and viability. Thus, local opening of chromatin by interactions between pioneer factors and core histones is crucial for genetic programming. SOURCE: Gregory DonahueZaret Lab The University of Pennsylvania
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