| RRC ID |
67197
|
| 著者 |
Jaiswal PK, Aljebali L, Gaumond MH, Oh CD, Yasuda H, Moffatt P.
|
| タイトル |
Biochemical characteristics of the chondrocyte-enriched SNORC protein and its transcriptional regulation by SOX9.
|
| ジャーナル |
Sci Rep
|
| Abstract |
Snorc (Small NOvel Rich in Cartilage) has been identified as a chondrocyte-specific gene in the mouse. Yet little is known about the SNORC protein biochemical properties, and mechanistically how the gene is regulated transcriptionally in a tissue-specific manner. The goals of the present study were to shed light on those important aspects. The chondrocyte nature of Snorc expression was confirmed in mouse and rat tissues, in differentiated (day 7) ATDC5, and in RCS cells where it was constitutive. Topological mapping and biochemical analysis brought experimental evidences that SNORC is a type I protein carrying a chondroitin sulfate (CS) attached to serine 44. The anomalous migration of SNORC on SDS-PAGE was due to its primary polypeptide features, suggesting no additional post-translational modifications apart from the CS glycosaminoglycan. A highly conserved SOX9-binding enhancer located in intron 1 was necessary to drive transcription of Snorc in the mouse, rat, and human. The enhancer was active independently of orientation and whether located in a heterologous promoter or intron. Crispr-mediated inactivation of the enhancer in RCS cells caused reduction of Snorc. Transgenic mice carrying the intronic multimerized enhancer drove high expression of a βGeo reporter in chondrocytes, but not in the hypertrophic zone. Altogether these data confirmed the chondrocyte-specific nature of Snorc and revealed dependency on the intronic enhancer binding of SOX9 for transcription.
|
| 巻・号 |
10(1)
|
| ページ |
7790
|
| 公開日 |
2020-5-8
|
| DOI |
10.1038/s41598-020-64640-x
|
| PII |
10.1038/s41598-020-64640-x
|
| PMID |
32385306
|
| PMC |
PMC7210984
|
| MeSH |
Amino Acid Sequence
Animals
Base Sequence
Cell Line
Cells, Cultured
Chondrocytes / metabolism*
Chondroitin Sulfates / metabolism
Gene Expression Regulation*
Humans
Membrane Proteins / chemistry
Membrane Proteins / genetics*
Membrane Proteins / metabolism*
Mice
Mice, Transgenic
Open Reading Frames
Protein Binding
Protein Domains
Proteoglycans / chemistry
Proteoglycans / genetics*
Proteoglycans / metabolism*
Rats
SOX9 Transcription Factor / metabolism*
Transcription Initiation Site
Transcription, Genetic
|
| IF |
3.998
|
| リソース情報 |
| ヒト・動物細胞 |
ATDC5(RCB0565) |
