Abstract
Skeletal muscle formation is controlled by multiple processes. These processes are tightly regulated by muscle regulatory factors. Genes that are highly and specifically expressed during myogenesis need to be identified. In the present study, the role of an anti-adipogenic gene adipose (Adp) in myogenesis is demonstrated. We discover that the expression of Adp is increased during myoblast differentiation. Overexpression of Adp in mouse myoblast C2C12 cells leads to an increase of myogenesis and up-regulation of MyoG expression. The inhibition effect of tumor necrosis factor α (TNFα) on myogenic differentiation is reversed by Adp-overexpression. Further research showed that TNFα significantly decreases Adp expression at both the mRNA and protein levels. Luciferase reporter assays showed that TNFα can inhibit Adp gene promoter activity and impair gene transcription. KLF15 was found to regulate the transcription of Adp. Furthermore, the expression of KLF15 and its binding to Adp promoter were reduced due to TNFα treatment. The reduced KLF15 expression after TNFα treatment is responsible for the repression of Adp gene promoter activity. KLF15 was also found to participate in Adp-mediated myogenic differentiation. Taken together, these data identify Adp as a positive modulator of myoblast differentiation and provide new insights for Adp function research. © 2014 Elsevier B.V.
| Original language | English |
|---|---|
| Pages (from-to) | 1183-1195 |
| Journal | Biochimica et Biophysica Acta - Gene Regulatory Mechanisms |
| Volume | 1839 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 1 Aug 2014 |
Bibliographical note
Publication details (e.g. title, author(s), publication statuses and dates) are captured on an “AS IS” and “AS AVAILABLE” basis at the time of record harvesting from the data source. Suggestions for further amendments or supplementary information can be sent to [email protected].Funding
This work was supported by grants from the National Key Basic Research Program of China ( 2012CB124702 ), 948 Program ( 2012-S13 ), Specialized Research Fund for the Doctoral Program of Higher Education ( 20110146130002 ), Program of National Natural Science Foundation of China ( 31172093 , 30970356 ), the National Science Foundation for Fostering Talents in Basic Research ( J1103510 ), and Huazhong Agricultural University Scientific and Technological Self-innovation Foundation ( 2013PY005 ).
Research Keywords
- Adipose (Adp)
- KLF15
- Myogenesis
- TNFα
- Transcriptional regulation
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