Premium
Targeted epigenetic modulation using a DNA‐based histone deacetylase inhibitor enhances cardiomyogenesis in mouse embryonic stem cells
Author(s) -
Lee JinA,
An Jieun,
Taniguchi Junichi,
Kashiwazaki Gengo,
Pandian Ganesh N.,
Parveen Nazia,
Kang Tong Mook,
Sugiyama Hiroshi,
De Debojyoti,
Kim Kyeong Kyu
Publication year - 2021
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.30140
Subject(s) - epigenetics , epigenome , histone deacetylase , downregulation and upregulation , histone deacetylase inhibitor , epigenomics , microbiology and biotechnology , histone , chemistry , biology , reporter gene , gene , dna methylation , cancer research , gene expression , genetics
Abstract The epigenome has an essential role in orchestrating transcriptional activation and modulating key developmental processes. Previously, we developed a library of pyrrole‐imidazole polyamides (PIPs) conjugated with suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor, for the purpose of sequence‐specific modification of epigenetics. Based on the gene expression profile of SAHA‐PIPs and screening studies using the α‐myosin heavy chain promoter‐driven reporter and SAHA–PIP library, we identified that SAHA–PIP G activates cardiac‐related genes. Studies in mouse ES cells showed that SAHA–PIP G could enhance the generation of spontaneous beating cells, which is consistent with upregulation of several cardiac‐related genes. Moreover, ChIP‐seq results confirmed that the upregulation of cardiac‐related genes is highly correlated with epigenetic activation, relevant to the sequence‐specific binding of SAHA–PIP G. This proof‐of‐concept study demonstrating the applicability of SAHA–PIP not only improves our understanding of epigenetic alterations involved in cardiomyogenesis but also provides a novel chemical‐based strategy for stem cell differentiation.