Project description:The transcription factor Sox9 (Sry-Related HMG-Box gene 9) is essential in chondrogenesis. The expression Sox9 is regulated by 1.5Mb long range genomic region in temporospatial manner and genome translocation or deletion which affect Sox9 expression cause campomelic dysplasia (CD), characterized by skeletal malformations. Although functional mechanism of Sox9 are well studied so far, regulatory mechanism of Sox9 expression and its related enhancer in chondrocytes are largely remains to be elucidated. The purpose of this study is to identify Sox9 enhancers in chondrocytes
Project description:The transcription factor Sox9 (Sry-Related HMG-Box gene 9) is essential in chondrogenesis. The expression Sox9 is regulated by 1.5Mb long range genomic region in temporospatial manner and genome translocation or deletion which affect Sox9 expression cause campomelic dysplasia (CD), characterized by skeletal malformations. Although functional mechanism of Sox9 are well studied so far, regulatory mechanism of Sox9 expression and its related enhancer in chondrocytes are largely remains to be elucidated. The purpose of this study is to identify Sox9 enhancers in chondrocytes
Project description:The transcription factor Sox9 (Sry-Related HMG-Box gene 9) is essential in chondrogenesis. The expression Sox9 is regulated by 1.5Mb long range genomic region in temporospatial manner and genome translocation or deletion which affect Sox9 expression cause campomelic dysplasia (CD), characterized by skeletal malformations. Although functional mechanism of Sox9 are well studied so far, regulatory mechanism of Sox9 expression and its related enhancer in chondrocytes are largely remains to be elucidated. The purpose of this study is to identify Sox9 enhancers in chondrocytes
Project description:We compared Sox9-association at chondrocyte targets to a broad catalogue of regulatory indicators of chromatin organization and transcriptional activity to determine Sox9’s direct regulatory actions in normal developing chondrocytes. Sox9-associated regions resolve into two distinct regulatory categories. Class I regions closely associate with transcriptional start sites (TSSs). Their targets reflect general regulators of basal cell activities that Sox9 engages indirectly though a likely association with the basal transcriptional complex. In contrast, Class II regions outside of the local TSS domains highlight evolutionarily conserved, active enhancers directing expression of chondrocyte specific target genes, though DNA binding of Sox9-dimers at target sites with sub-optimal binding affinity. The level of associated chondrocyte gene expression correlates with the number of enhancer modules around the target gene and grouping into super-enhancer clusters. Comparison of Sox9 programs between neural crest and mesoderm-derived chondrocytes points to similar modes of chondrocyte specification in distinct chondrocyte lineages. These data provide the first insight into mammalian Sox family actions at the genome scale in the vivo setting. The resulting enhancer sets provide a key resource for further dissection of the regulatory programs of mammalian chondrogenesis. Incorportation of ChIP-seq data of Sox9 and histone modification marks for chromatin status together with microrarray gene expression profiling in neonatal mice chondrocytes to uncover Sox9 regulatory system
Project description:Chondrocytes undergo a series of sequential differentiation steps which result in the formation of a unique hierarchical columnar structure including proliferating, pre-hypertrophic and hypertrophic chondrocytes. Pre-hypertrophic chondrocytes, which exist in the transitional stage between proliferating and hypertrophic chondrocytes, are a rare cell population in the growth plate but critical for endochondral bone development. However, the molecular basis of pre-hypertrophic chondrocytes largely remains elusive. The purpose of this study is to identify novel marker gene and uncover regulatory mechanism of marker gene expression.
Project description:We compared Sox9-association at chondrocyte targets to a broad catalogue of regulatory indicators of chromatin organization and transcriptional activity to determine Sox9’s direct regulatory actions in normal developing chondrocytes. Sox9-associated regions resolve into two distinct regulatory categories. Class I regions closely associate with transcriptional start sites (TSSs). Their targets reflect general regulators of basal cell activities that Sox9 engages indirectly through a likely association with the basal transcriptional complex. In contrast, Class II regions outside of the local TSS domains highlight evolutionarily conserved, active enhancers directing expression of chondrocyte specific target genes, though DNA binding of Sox9-dimers at target sites with sub-optimal binding affinity. The level of associated chondrocyte gene expression correlates with the number of enhancer modules around the target gene and grouping into super-enhancer clusters. Comparison of Sox9 programs between neural crest and mesoderm-derived chondrocytes points to similar modes of chondrocyte specification in distinct chondrocyte lineages. These data provide the first insight into mammalian Sox family actions at the genome scale in the vivo setting. The resulting enhancer sets provide a key resource for further dissection of the regulatory programs of mammalian chondrogenesis. Incorportation of ChIP-seq data of Sox9 and histone modification marks for chromatin status together with micorarray gene expression profiling in neonatal mice chondrocytes to uncover Sox9 regulatory system. Overexpression of Sox9 with a control of EGFP in human fibroblasts to identify the direct targets of Sox9 regulatory system