Temporally discordant chromatin accessibility and DNA demethylation define short and long-term enhancer regulation during cell fate specification.

ABSTRACT: Epigenetic mechanisms govern the transcriptional activity of lineage-specifying enhancers; but recent work challenges the dogma that joint chromatin accessibility and DNA demethylation are prerequisites for transcription. To understand this paradox, we established a highly-resolved timeline of DNA demethylation, chromatin accessibility, and transcription factor occupancy during neural progenitor cell differentiation. We show thousands of enhancers undergo rapid, transient accessibility changes associated with distinct periods of transcription factor expression. However, most DNA methylation changes are unidirectional and delayed relative to chromatin dynamics, creating transiently discordant epigenetic states. Genome-wide detection of 5-hydroxymethylcytosine further revealed active demethy

SUBMITTER: Guerin LN 

PROVIDER: S-EPMC11383056 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature