Distinct Transcriptional Programs Underlie Sox9 Regulation of the Mammalian Chondrocyte
Sox9 encodes an essential transcriptional regulator of chondrocyte specification and differentiation. When Sox9 nuclear activity was compared with markers of chromatin organization and transcriptional activity in primary chondrocytes, we identified two distinct categories of target association. Clas...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2015-07-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124715006117 |
| _version_ | 1818992236665241600 |
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| author | Shinsuke Ohba Xinjun He Hironori Hojo Andrew P. McMahon |
| author_facet | Shinsuke Ohba Xinjun He Hironori Hojo Andrew P. McMahon |
| author_sort | Shinsuke Ohba |
| collection | DOAJ |
| description | Sox9 encodes an essential transcriptional regulator of chondrocyte specification and differentiation. When Sox9 nuclear activity was compared with markers of chromatin organization and transcriptional activity in primary chondrocytes, we identified two distinct categories of target association. Class I sites cluster around the transcriptional start sites of highly expressed genes with no chondrocyte-specific signature. Here, Sox9 association reflects protein-protein association with basal transcriptional components. Class II sites highlight evolutionarily conserved active enhancers that direct chondrocyte-related gene activity through the direct binding of Sox9 dimer complexes to DNA. Sox9 binds through sites with sub-optimal binding affinity; the number and grouping of enhancers into super-enhancer clusters likely determines the levels of target gene expression. Interestingly, comparison of Sox9 action in distinct chondrocyte lineages points to similar regulatory strategies. In addition to providing insights into Sox family action, our comprehensive identification of the chondrocyte regulatory genome will facilitate the study of skeletal development and human disease. |
| first_indexed | 2024-12-20T20:22:57Z |
| format | Article |
| id | doaj.art-bf7fef698bda4e3e87f560b54d32a61e |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-20T20:22:57Z |
| publishDate | 2015-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-bf7fef698bda4e3e87f560b54d32a61e2022-12-21T19:27:32ZengElsevierCell Reports2211-12472015-07-0112222924310.1016/j.celrep.2015.06.013Distinct Transcriptional Programs Underlie Sox9 Regulation of the Mammalian ChondrocyteShinsuke Ohba0Xinjun He1Hironori Hojo2Andrew P. McMahon3Department of Bioengineering, the University of Tokyo Graduate School of Engineering, Tokyo 113-0033, JapanDepartment of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad-CIRM Center for Regenerative Medicine and Stem Cell Research, W.M. Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USADepartment of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad-CIRM Center for Regenerative Medicine and Stem Cell Research, W.M. Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USADepartment of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad-CIRM Center for Regenerative Medicine and Stem Cell Research, W.M. Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USASox9 encodes an essential transcriptional regulator of chondrocyte specification and differentiation. When Sox9 nuclear activity was compared with markers of chromatin organization and transcriptional activity in primary chondrocytes, we identified two distinct categories of target association. Class I sites cluster around the transcriptional start sites of highly expressed genes with no chondrocyte-specific signature. Here, Sox9 association reflects protein-protein association with basal transcriptional components. Class II sites highlight evolutionarily conserved active enhancers that direct chondrocyte-related gene activity through the direct binding of Sox9 dimer complexes to DNA. Sox9 binds through sites with sub-optimal binding affinity; the number and grouping of enhancers into super-enhancer clusters likely determines the levels of target gene expression. Interestingly, comparison of Sox9 action in distinct chondrocyte lineages points to similar regulatory strategies. In addition to providing insights into Sox family action, our comprehensive identification of the chondrocyte regulatory genome will facilitate the study of skeletal development and human disease.http://www.sciencedirect.com/science/article/pii/S2211124715006117 |
| spellingShingle | Shinsuke Ohba Xinjun He Hironori Hojo Andrew P. McMahon Distinct Transcriptional Programs Underlie Sox9 Regulation of the Mammalian Chondrocyte Cell Reports |
| title | Distinct Transcriptional Programs Underlie Sox9 Regulation of the Mammalian Chondrocyte |
| title_full | Distinct Transcriptional Programs Underlie Sox9 Regulation of the Mammalian Chondrocyte |
| title_fullStr | Distinct Transcriptional Programs Underlie Sox9 Regulation of the Mammalian Chondrocyte |
| title_full_unstemmed | Distinct Transcriptional Programs Underlie Sox9 Regulation of the Mammalian Chondrocyte |
| title_short | Distinct Transcriptional Programs Underlie Sox9 Regulation of the Mammalian Chondrocyte |
| title_sort | distinct transcriptional programs underlie sox9 regulation of the mammalian chondrocyte |
| url | http://www.sciencedirect.com/science/article/pii/S2211124715006117 |
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