Pioneer transcription factors bind silent condensed chromatin early in a developmental programme prior to target gene activation, either to open up local chromatin, imparting competence to other transcriptional activators to initiate a developmental lineage, or to directly facilitate other factors binding to nucleosomal DNA; and they may also demethylate tissue-specific regions of DNA, to generate stable lineage-specific DNA methylation patterns to enhance gene expression. This project will investigate the mechanisms of the Foxa family of transcription factors in their regulation of T-cell development and investigate how they influence TCR repertoire diversity.
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