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- Title
Histone methyltransferase ASH1 orchestrates fibrogenic gene transcription during myofibroblast transdifferentiation.
- Authors
Perugorria, Maria Jesus; Wilson, Caroline L; Zeybel, Mujdat; Walsh, Meagan; Amin, Shilu; Robinson, Stuart; White, Steven A; Burt, Alastair D; Oakley, Fiona; Tsukamoto, Hidekazu; Mann, Derek A; Mann, Jelena
- Abstract
Transdifferentiation of hepatic stellate cells (HSCs) to a myofibroblast-like phenotype is the pivotal event in liver fibrosis. The dramatic change in phenotype associated with transdifferentiation is underpinned by a global change in gene expression. Orchestrated changes in gene expression take place at the level of chromatin packaging which is regulated by enzymatic activity of epigenetic regulators that in turn affect histone modifications. Using expression profiling of epigenetic regulators in quiescent and activated primary HSCs we found a number of histone methyltransferases including MLL1, MLL5, Set1 and ASH1 to be highly up-regulated during transdifferentiation of HSCs. All of these histone methyltransferases regulate methylation of lysine 4 of histone H3, which is a signature of actively transcribed genes. We therefore postulated that one or more of these enzymes may be involved in positively influencing expression of profibrogenic genes.
- Publication
Hepatology (Baltimore, Md.), 2012, Vol 56, Issue 3, p1129
- ISSN
1527-3350
- Publication type
Journal Article
- DOI
10.1002/hep.25754