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Sci Rep. 2016 Oct 18;6:35355. doi: 10.1038/srep35355.

Dnmt1 regulates the myogenic lineage specification of muscle stem cells.

Liu R1,2,3, Kim KY1, Jung YW1,4, Park IH1.

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Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven, CT, 06520.
Agnes Ginges Laboratory for Diseases of the Aorta, Centenary Institute, University of Sydney, Camperdown, 2042, Australia.
Sydney Medical School, University of Sydney, Sydney, 2006, Australia.
Department of Obstetrics and Gynecology, CHA Gangnam Medical Center, CHA University, Seoul, Republic of Korea.


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.

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