Distinct Transcriptional Programs Underlie Sox9 Regulation of the Mammalian Chondrocyte
Year: 2015
Type: article
Abstract: 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.
Source: Cell Reports
Institutions: The University of Tokyo, University of Southern California
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Awards: Identification of the molecular network regulating movement of Hedgehog proteins on cell surface during skeletal development, Developmental Regulation of Bone Morphogenesis, Development of a novel strategy for bone regeneration with small molecule-mediated osteo-reprogramming and understanding of genomic mechanisms underlying the process, Dynamics of epigenome and transcription during the Hedgehog signaling-mediated specification of skeletal cells
OpenAlex ID: W1849784044