Methylation Mesa define functional regulatory elements for targeted gene activation.

ABSTRACT: DNA methylation and mRNA expression correlations are often presented with inconsistent evidence supporting causal regulation. We hypothesized that causal regulatory methylation elements would exhibit heightened demethylation sensitivity. To investigate, we analyzed 20 whole-genomic bisulfite sequenced samples before and after demethylation and identified narrow-width (45-294 bp) elements within a short plateau, termed Methylation Mesa (MM). The Mesa signature was conserved across species and was independent of CpG islands. Mesa also demonstrate high concordance with primed and active histone marks. To assess causality, we developed CRISPR-DiR, a highly precise targeted demethylation technology. Targeted demethylation of a Mesa triggers locus and distal chromatin rewiring events that initia

SUBMITTER: Liu YV 

PROVIDER: S-EPMC11527235 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature