H3K4 di-methylation governs smooth muscle lineage identity and promotes vascular homeostasis by restraining plasticity.

ABSTRACT: Epigenetic mechanisms contribute to the regulation of cell differentiation and function. Vascular smooth muscle cells (SMCs) are specialized contractile cells that retain phenotypic plasticity even after differentiation. Here, by performing selective demethylation of histone H3 lysine 4 di-methylation (H3K4me2) at SMC-specific genes, we uncovered that H3K4me2 governs SMC lineage identity. Removal of H3K4me2 via selective editing in cultured vascular SMCs and in murine arterial vasculature led to loss of differentiation and reduced contractility due to impaired recruitment of the DNA methylcytosine dioxygenase TET2. H3K4me2 editing altered SMC adaptative capacities during vascular remodeling due to loss of miR-145 expression. Finally, H3K4me2 editing induced a profound alteration of SMC lin

SUBMITTER: Liu M 

PROVIDER: S-EPMC8567421 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature