Large-scale manipulation of promoter DNA methylation reveals context-specific transcriptional responses and stability.

ABSTRACT:

Background

Cytosine DNA methylation is widely described as a transcriptional repressive mark with the capacity to silence promoters. Epigenome engineering techniques enable direct testing of the effect of induced DNA methylation on endogenous promoters; however, the downstream effects have not yet been comprehensively assessed.

Results

Here, we simultaneously induce methylation at thousands of promoters in human cells using an engineered zinc finger-DNMT3A fusion protein, enabling us to test the effect of forced DNA methylation upon transcription, chromatin accessibility, histone modifications, and DNA methylation persistence after the removal of the fusion protein. We find that transcriptional responses to DNA methylation are highly context-specific, including lack of repre

SUBMITTER: de Mendoza A 

PROVIDER: S-EPMC9316731 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature