Exp Mol Med.
2018 Jan;50(1):e427. 10.1038/emm.2017.236.
Sumoylation of histone deacetylase 1 regulates MyoD signaling during myogenesis
- Affiliations
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- 1Department of Pharmacology, Chonnam National University Medical School, Jeollanamdo, Republic of Korea. eomgh@jnu.ac.kr, kookhyun@jnu.ac.kr
- 2Basic Research Laboratory for Cardiac Remodeling, Chonnam National University Medical School, Jeollanamdo, Republic of Korea.
- 3Center for Creative Biomedical Scientists at Chonnam National University, Jeollanamdo, Republic of Korea.
- 4Medical Research Center for Gene Regulation, Chonnam National University Medical School, Jeollanamdo, Republic of Korea.
- 5Department of Surgery, Chonnam National University Hospital, Gwangju, Republic of Korea.
- 6Department of Biochemistry, Chonnam National University Medical School, Jeollanamdo, Republic of Korea.
- KMID: 2438357
- DOI: http://doi.org/10.1038/emm.2017.236
Abstract
- Sumoylation, the conjugation of a small ubiquitin-like modifier (SUMO) protein to a target, has diverse cellular effects. However, the functional roles of the SUMO modification during myogenesis have not been fully elucidated. Here, we report that basal sumoylation of histone deacetylase 1 (HDAC1) enhances the deacetylation of MyoD in undifferentiated myoblasts, whereas further sumoylation of HDAC1 contributes to switching its binding partners from MyoD to Rb to induce myocyte differentiation. Differentiation in C2C12 skeletal myoblasts induced new immunoblot bands above HDAC1 that were gradually enhanced during differentiation. Using SUMO inhibitors and sumoylation assays, we showed that the upper band was caused by sumoylation of HDAC1 during differentiation. Basal deacetylase activity was not altered in the SUMO modification-resistant mutant HDAC1 K444/476R (HDAC1 2R). Either differentiation or transfection of SUMO1 increased HDAC1 activity that was attenuated in HDAC1 2R. Furthermore, HDAC1 2R failed to deacetylate MyoD. Binding of HDAC1 to MyoD was attenuated by K444/476R. Binding of HDAC1 to MyoD was gradually reduced after 2 days of differentiation. Transfection of SUMO1 induced dissociation of HDAC1 from MyoD but potentiated its binding to Rb. SUMO1 transfection further attenuated HDAC1-induced inhibition of muscle creatine kinase luciferase activity that was reversed in HDAC1 2R. HDAC1 2R failed to inhibit myogenesis and muscle gene expression. In conclusion, HDAC1 sumoylation plays a dual role in MyoD signaling: enhancement of HDAC1 deacetylation of MyoD in the basally sumoylated state of undifferentiated myoblasts and dissociation of HDAC1 from MyoD during myogenesis.
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