Epigenetic mechanisms and developmental choice hierarchies in T-lymphocyte development

Abstract

Three interlocking problems in gene regulation are: how to explain genome-wide targeting of transcription factors in different cell types, how prior transcription factor action can establish an ‘epigenetic state’ that changes the options for future transcription factor action, and how directly a sequence of developmental decisions can be memorialized in a hierarchy of repression structures applied to key genes of the ‘paths not taken’. This review uses the finely staged process of T-cell lineage commitment as a test case in which to examine how changes in developmental status are reflected in changes in transcription factor expression, transcription factor binding distribution across genomic sites, and chromatin modification. These are evaluated in a framework of reciprocal effects of previous chromatin structure features on transcription factor access and of transcription factor binding on other factors and on future chromatin structure.