YY2 Promotes Osteoblast Differentiation by Upregulating Osterix Transcriptional Activity
Yin Yang 2 (YY2) is a paralog of YY1, a well-known multifunctional transcription factor containing a C-terminal zinc finger domain. Although the role of YY1 in various biological processes, such as the cell cycle, cell differentiation and tissue development, is well established, the function of YY2...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-04-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/8/4303 |
| Summary: | Yin Yang 2 (YY2) is a paralog of YY1, a well-known multifunctional transcription factor containing a C-terminal zinc finger domain. Although the role of YY1 in various biological processes, such as the cell cycle, cell differentiation and tissue development, is well established, the function of YY2 has not been fully determined. In this study, we investigated the functional role of YY2 during osteoblast differentiation. <i>YY2</i> overexpression and knockdown increased and decreased osteoblast differentiation, respectively, in BMP4-induced C2C12 cells. Mechanistically, <i>YY2</i> overexpression increased the mRNA and protein levels of Osterix (Osx), whereas <i>YY2</i> knockdown had the opposite effect. To investigate whether YY2 regulates <i>Osx</i> transcription, the effect of <i>YY2</i> overexpression and knockdown on <i>Osx</i> promoter activity was evaluated. <i>YY2</i> overexpression significantly increased <i>Osx</i> promoter activity in a dose-dependent manner, whereas <i>YY2</i> knockdown had the opposite effect. Furthermore, vectors containing deletion and point mutations were constructed to specify the regulation site. Both the Y1 and Y2 sites were responsible for YY2-mediated <i>Osx</i> promoter activation. These results indicate that YY2 is a positive regulator of osteoblast differentiation that functions by upregulating the promoter activity of <i>Osx</i>, a representative osteogenic transcription factor in C2C12 cells. |
|---|---|
| ISSN: | 1661-6596 1422-0067 |