tailieunhanh - Báo cáo khoa hoc : Tip60 regulates myoblast differentiation by enhancing the transcriptional activity of MyoD via their physical interactions

The progression of muscle differentiation is tightly controlled by multiple groups of transcription factors and transcriptional coregulators. MyoD is a transcription factor of the myogenic basic helix–loop–helix family required for the process of muscle cell differentiation. | IFEBS Journal Tip60 regulates myoblast differentiation by enhancing the transcriptional activity of MyoD via their physical interactions Jung-Woong Kim Sang-Min Jang Chul-Hong Kim Joo-Hee An Eun-Jin Kang and Kyung-Hee Choi Department of Life Science BK21 program College of NaturalSciences Chung-Ang University Seoul Korea Keywords MyoD myogenesis protein-protein interaction Tip60 transcriptionalregulation Correspondence . Choi Department of Life Science BK21 program College of Natural Sciences Chung-Ang University 221 Heuksuk Dong Dongjak Ku Seoul156-756 Korea Fax 82 2 824 7302 Tel 82 2 820 5209 E-mail khchoi@ These authors contributed equally to this work Received 5 May 2011 revised 20 August 2011 accepted 15 September 2011 doi The progression of muscle differentiation is tightly controlled by multiple groups of transcription factors and transcriptional coregulators. MyoD is a transcription factor of the myogenic basic helix-loop-helix family required for the process of muscle cell differentiation. We now show that Tip60 is required for myoblast differentiation via enhancement of the transcriptional activity of MyoD. Knockdown of Tip60 in C2C12 cells leads to a lack of ability to switch from proliferating myoblasts to differentiated myotubes. Ectopic expression of Tip60 increased MyoD-mediated luciferase activity on the myogenic regulatory gene myogenin. We also found that Tip60 physically interacts with MyoD using its chromo- and Zn-finger-containing region and that these protein interactions were required for the effective transcriptional activation of MyoD. Furthermore a chromatin immunoprecipitation assay revealed that Tip60 recruits MyoD on the myogenin promoter and Tip60 also increases the levels of acetylated histones H3 and H4 during myogenic differentiation. Taken together these findings suggest that Tip60 is an important co-activator for MyoD-mediated myogenesis in mouse myoblast C2C12 cells. Structured .