MeCP2 controls an epigenetic pathway that promotes myofibroblast transdifferentiation and fibrosis.

ABSTRACT:

Background & aims

Myofibroblast transdifferentiation generates hepatic myofibroblasts, which promote liver fibrogenesis. The peroxisome proliferator-activated receptor gamma (PPARgamma) is a negative regulator of this process. We investigated epigenetic regulation of PPARgamma and myofibroblast transdifferentiation.

Methods

Chromatin immunoprecipitation (ChIP) assays assessed the binding of methyl-CpG binding protein 2 (MeCP2) to PPARgamma and chromatin modifications that silence this gene. MeCP2(-/y) mice and an inhibitor (DZNep) of the epigenetic regulatory protein EZH2 were used in the carbon tetrachloride model of liver fibrosis. Liver tissues from mice were assessed by histologic analysis; markers of fibrosis were measured by quantitative polymerase chain reaction (qPCR

SUBMITTER: Mann J 

PROVIDER: S-EPMC2819585 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature