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PMID: 21594584 Published · ppublish English Journal Article Review

Unraveling the transcriptional regulatory machinery in chondrogenesis.

Journal of bone and mineral metabolism ·Vol. 29 ·No. 4 ·2011-07-00 ·Pages 390-5

Akiyama H, Lefebvre V

Abstract

Since the discovery of SOX9 mutations in the severe human skeletal malformation syndrome campomelic dysplasia in 1994, Sox9 was shown to be both required and sufficient for chondrocyte specification and differentiation. At the same time, its distant relatives Sox5 and Sox6 were shown to act in redundancy with each other to robustly enhance its functions. The Sox trio is currently best known for its ability to activate the genes for cartilage-specific extracellular matrix components. Sox9 and Sox5/6 homodimerize through domains adjacent to their Sry-related high-mobility-group DNA-binding domain to increase the efficiency of their cooperative binding to chondrocyte-specific enhancers. Sox9 possesses a potent transactivation domain and thereby recruits diverse transcriptional co-activators, histone-modifying enzymes, subunits of the mediator complex, and components of the general transcriptional machinery, such as CBP/p300, Med12, Med25, and Wwp2. This information helps us begin to unravel the mechanisms responsible for Sox9-mediated transcription. We review here the discovery of this master chondrogenic trio and its roles in chondrogenesis in vivo and at the molecular level, and we discuss how these pioneering studies open the way for many additional studies that are needed to further increase our understanding of the transcriptional regulatory machinery operating in chondrogenesis.

MeSH Terms
Chondrogenesis/genetics Gene Expression Regulation Humans SOX Transcription Factors/metabolism Transcription, Genetic
Chemicals
SOX Transcription Factors
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Akiyama Haruhiko
Department of Orthopaedics, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo, Kyoto 606-8507, Japan. hakiyama@kuhp.kyoto-u.ac.jp
Lefebvre Véronique
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Article Info
Journal
Journal of bone and mineral metabolism
Abbr.
J Bone Miner Metab
ISSN
1435-5604
DOI
10.1007/s00774-011-0273-9
Email
hakiyama@kuhp.kyoto-u.ac.jp
Published
2011-07-00
Epub
2011-00-19
Pages
390-5
Language
English
Region
Japan
NLM ID
9436705
PMCID
PMC3354916
Subset
IM
Grants
NIAMS NIH HHS · R01 AR046249 · United States
NIAMS NIH HHS · R01 AR054153 · United States
NIAMS NIH HHS · R01 AR060016 · United States
External Links
PubMed source DOI: 10.1007/s00774-011-0273-9 PMC Full Text View journal details
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