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c‐Ski activates MyoD in the nucleus of myoblastic cells through suppression of histone deacetylases
Author(s) -
Kobayashi Norihiko,
Goto Kouichiro,
Horiguchi Kana,
Nagata Motoko,
Kawata Mikiko,
Miyazawa Keiji,
Saitoh Masao,
Miyazono Kohei
Publication year - 2007
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2007.01052.x
Subject(s) - myod , myogenin , biology , pitx2 , myod protein , mef2 , transcription factor , myogenesis , microbiology and biotechnology , enhancer , myogenic regulatory factors , myf5 , myocyte , genetics , gene , homeobox
c‐Ski, originally identified as an oncogene product, induces myogenic differentiation in nonmyogenic fibroblasts through transcriptional activation of muscle regulatory factors. Although c‐Ski does not bind to DNA directly, it binds to DNA through interaction with Smad proteins and regulates signaling activities of transforming growth factor‐β (TGF‐β). In the present study, we show that c‐Ski activates the myogenin promoter independently of regulation of endogenous TGF‐β signaling. Expression of myogenin is regulated by a transcription factor complex containing proteins of the MyoD family and the myocyte enhancer factor 2 (MEF2) family. c‐Ski acts on the MyoD–MEF2 complex and modulates the activity of MyoD in myogenin promoter regulation. Interestingly, histone deacetylase (HDAC) inhibitors up‐regulated basal activity of transcription from a MyoD‐responsive reporter, although c‐Ski failed to further augment this transcription in the presence of HDAC inhibitors. c‐Ski is observed both in the cytoplasm and in the nucleus, but its nuclear localization is required for myogenic differentiation. We conclude that c‐Ski induces myogenic differentiation through acting on MyoD and inhibiting HDAC activity in the nucleus of myogenic cells.