Pluto Bioinformatics

GSE131366: Distinct Contribution of DNA Methylation and Histone Acetylation to the Genomic Occupancy of Transcription Factors

Bulk RNA sequencing

DNA methylation has been shown to act by directly modulating transcription factor affinity to DNA binding sites and by recruiting methyl-CpG binding proteins, which form complexes with histone deacetylases (HDACs). Both mechanisms can affect gene regulation, but the extent to which HDACs contribute to the function of DNA methylation and transcription factor occupancy is not clear. To address this question we measured gene expression alterations, chromatin accessibility and transcription factor occupancy in wild type or DNA methylation-deficient mouse embryonic stem cells following HDAC inhibition. We observe widespread elevated chromatin accessibility at repeat elements following histone hyper-acetylation, which was magnified by the absence of DNA methylation. Subsets of repeat elements displayed enriched binding by distinct transcription factors and elevated expression. The pronounced additive effect of HDAC inhibition in DNA methylation deficient cells demonstrate that DNA methylation and histone deacetylation act largely independently to supress transcription factor binding and gene expression. SOURCE: Skirmantas Kriaucionis (skirmantas.kriaucionis@ludwig.ox.ac.uk) - Ludwig Cancer Research Oxford