Open AccessDnmt1 regulates the myogenic lineage specification of muscle stem cells
Author(s) -
Renjing Liu,
Kun-Yong Kim,
Yong-Wook Jung,
InHyun Park
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep35355
Subject(s) - myogenesis , dna methylation , dnmt1 , biology , epigenetics , microbiology and biotechnology , myocyte , transdifferentiation , conditional gene knockout , cellular differentiation , c2c12 , regulation of gene expression , genetics , stem cell , gene expression , gene , phenotype
DNA methylation is an important epigenetic mark that regulates gene expression. Dnmt1 plays an important role in maintaining DNA methylation patterns on daughter DNA strands. Studies have shed light into the functional role of Dnmt1 regulation in the hematopoietic and epidermal systems. Here we show that Dnmt1 is required for myogenesis. Loss of Dnmt1 results in reduced expression of myogenic genes and defects in myogenic differentiation. We have utilized a conditional knockout mouse approach to examine the functional consequences of Dnmt1 depletion specifically in the developing muscle. These mice were born runted, with smaller body weights, and reduced ability to form myotubes in vitro . We show that expression of Id-1, a negative regulator of myogenesis, is enhanced in Dnmt1-deficient cultures, leading to enhanced transdifferentiation of myoblasts toward the osteogenic lineage. Thus, these studies demonstrate that Dnmt1 influences cellular identity and determines lineage fidelity.