Open AccessHistone modifications interact with DNA methylation at the GATA 4 promoter during differentiation of mesenchymal stem cells into cardiomyocyte‐like cells
Author(s) -
Xu Hao,
Yi Qin,
Yang Chunmei,
Wang Yue,
Tian Jie,
Zhu Jing
Publication year - 2016
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12253
Subject(s) - mesenchymal stem cell , microbiology and biotechnology , dna methylation , histone , methylation , biology , chemistry , dna , biochemistry , gene , gene expression
Objectives A previous study of ours confirmed that Islet‐1 specifically induces differentiation of MSC s into cardiomyocytes, and that one of the mechanisms underlying that process is regulation of histone acetylation. Here, we further explore the mechanism of MSC differentiation into cardiomyocytes from the perspective of interactions between epigenetic modifications. Materials and methods We used lentiviral vectors to overexpress Islet‐1 in MSC s, and Ch IP ‐ qPCR , MSP and BSP were performed to detect levels of histone acetylation/methylation and DNA methylation in the GATA 4 and Nkx2.5 promoters. To further explore relationships between these epigenetic modifications, we used 5‐aza or TSA to interfere with DNA methylation and histone acetylation, respectively, and detected effects on the other two modifications. Results Histone acetylation level increased and its methylation level decreased at GATA 4 and Nkx2.5 promoters; DNA methylation level was reduced at the GATA 4 promoter but did not change at the Nkx2.5 promoter. Furthermore, 5‐aza increased histone acetylation level and reduced its methylation level at the GATA 4 promoter but had no effect on the Nkx2.5 promoter; TSA reduced histone methylation and DNA methylation levels at the GATA 4 promoter, but it only reduced histone methylation level at the Nkx2.5 promoter. Conclusions Histone acetylation/methylation and DNA methylation were both involved in regulating GATA 4 expression, but Nkx2.5 expression was not regulated by DNA methylation. These three modifications had high correlation with each other during regulation of GATA 4 and produced a regulation loop at the GATA 4 promoter.