EP300 as a Molecular Integrator of Fibrotic Transcriptional Programs

Fibrosis is a condition characterized by the excessive accumulation of extracellular matrix proteins in tissues, leading to organ dysfunction and failure. Recent studies have identified EP300, a histone acetyltransferase, as a crucial regulator of the epigenetic changes that contribute to fibrosis. In fact, EP300-mediated acetylation of histones alters global chromatin structure and gene expression, promoting the development and progression of fibrosis. Here, we review the role of EP300-mediated epigenetic regulation in multi-organ fibrosis and its potential as a therapeutic target. We discuss the preclinical evidence that suggests that EP300 inhibition can attenuate fibrosis-related molecular processes, including extracellular matrix deposition, inflammation, and epithelial-to-mesenchymal transition. We also highlight the contributions of small molecule inhibitors and gene therapy approaches targeting EP300 as novel therapies against fibrosis.

Automated summary

Fibrosis is a pathological condition characterized by excessive deposition of extracellular matrix proteins in tissues, leading to organ dysfunction and failure. Recent studies have highlighted the role of the histone acetyltransferase EP300 in mediating epigenetic changes associated with fibrosis. EP300-mediated histone acetylation alters chromatin structure and gene expression, promoting fibrosis development and progression. This review discusses the involvement of EP300 in multi-organ fibrosis and its potential as a therapeutic target, including the use of small molecule inhibitors and gene therapy approaches.