Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-10-25
pubmed:abstractText
During myogenesis, transcriptional activities of two major myogenic factors, MyoD and myocyte enhancer factor 2 (Mef2) are regulated by histone modifications that switch on and off the target genes. However, the transition mechanism from repression to activation modes of histones has not been defined. Here we identify that lysine specific demethylase 1, (LSD1) is responsible for removing the repressive histone codes during C2C12 mouse myoblast differentiation. The potent role of LSD1 is suggested by the increment of its expression level during myogenic differentiation. Moreover, by performing co-immunoprecipitation and ChIP assay, physically interaction of LSD1 with MyoD and Mef2 on the target promoters was identified. Their interactions were resulted in upregulation of the transcription activities shown with increased luciferase activity. Interruption of demethylase activity of LSD1 using shRNA or chemical inhibitor, pargyline, treatment led to aberrant histone codes on myogenic promoters during skeletal muscle differentiation. We also demonstrate that inhibition of LSD1 impairs C2C12 mouse myoblast differentiation. Our results show for the first time the regulatory mechanism of myogenesis involving histone demethylase. Altogether, the present study suggests a de-repression model and expands the understanding on the dynamic regulation of chromatin during myogenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1090-2104
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
22
pubmed:volume
401
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
327-32
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Histone demethylase LSD1 is required to induce skeletal muscle differentiation by regulating myogenic factors.
pubmed:affiliation
National Research Laboratory for Metabolic Checkpoint, Departments of Biomedical Sciences and Biochemistry and Molecular Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't