Open AccessEpigenetics and expression of key genes associated with cardiac fibrosis:NLRP3, MMP2, MMP9, CCN2/CTGFandAGT
Author(s) -
Sruti Chandra,
Kenneth C. Ehrlich,
Michelle Lacey,
Carl Baribault,
Melanie Ehrlich
Publication year - 2021
Publication title -
epigenomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.265
H-Index - 60
eISSN - 1750-1911
pISSN - 1750-192X
DOI - 10.2217/epi-2020-0446
Subject(s) - ctgf , biology , enhancer , transcription factor , epigenetics , cardiac fibrosis , fibrosis , dna methylation , mmp9 , mmp2 , microbiology and biotechnology , chromatin remodeling , gene , epigenomics , gene expression , cancer research , genetics , growth factor , pathology , downregulation and upregulation , medicine , receptor
Aims: Excessive inflammatory signaling and pathological remodeling of the extracellular matrix drive cardiac fibrosis and require changes in gene expression. Materials and methods: Using bioinformatics, both tissue-specific expression profiles and epigenomic profiles of some genes critical for cardiac fibrosis were examined, namely, NLRP3, MMP2, MMP9, CCN2/CTGF, AGT (encodes angiotensin II precursors) and hsa-mir-223 (post-transcriptionally regulates NLRP3). Results: In monocytes, neutrophils, fibroblasts, venous cells, liver and brain, enhancers or super-enhancers were found that correlate with high expression of these genes. One enhancer extended into a silent gene neighbor. These enhancers harbored tissue-specific foci of DNA hypomethylation, open chromatin and transcription factor binding. Conclusions: This study identified previously undescribed enhancers containing hypomethylated transcription factor binding subregions that are predicted to regulate expression of these cardiac fibrosis-inducing genes.