title: SOX9 regulates multiple genes in chondrocytes, including genes encoding ECM proteins, ECM modification enzymes, receptors, and transporters.
abstract: The transcription factor SOX9 plays an essential role in determining the fate of several cell types and is a master factor in regulation of chondrocyte development. Our aim was to determine which genes in the genome of chondrocytes are either directly or indirectly controlled by SOX9. We used RNA-Seq to identify genes whose expression levels were affected by SOX9 and used SOX9 ChIP-Seq to identify those genes that harbor SOX9-interaction sites. For RNA-Seq, the RNA expression profile of primary Sox9flox/flox mouse chondrocytes infected with Ad-CMV-Cre was compared with that of the same cells infected with a control adenovirus. Analysis of RNA-Seq data indicated that, when the levels of Sox9 mRNA were decreased more than 8-fold by infection with Ad-CMV-Cre, 196 genes showed a decrease in expression of at least 4-fold. These included many cartilage extracellular matrix (ECM) genes and a number of genes for ECM modification enzymes (transferases), membrane receptors, transporters, and others. In ChIP-Seq, 75% of the SOX9-interaction sites had a canonical inverted repeat motif within 100 bp of the top of the peak. SOX9-interaction sites were found in 55% of the genes whose expression was decreased more than 8-fold in SOX9-depleted cells and in somewhat fewer of the genes whose expression was reduced more than 4-fold, suggesting that these are direct targets of SOX9. The combination of RNA-Seq and ChIP-Seq has provided a fuller understanding of the SOX9-controlled genetic program of chondrocytes.
authors.affiliation: Department of Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Chun-do
authors.initials: CD
authors.lastname: Oh
authors.affiliation: Department of Bioinformatics and Computational Science, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Yue
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Bioinformatics and Computational Science, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Shoudan
authors.initials: S
authors.lastname: Liang
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Mori-Akiyama
authors.affiliation: Department of Biochemistry, Rush University Medical Center, Chicago, Illinois, United States of America.
authors.forename: Di
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Benoit
authors.initials: B
authors.lastname: de Crombrugghe
authors.affiliation: Department of Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Hideyo
authors.initials: H
authors.lastname: Yasuda
mesh_terms: D000818:Animals; D001665:Binding Sites; D019902:Chondrocytes / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D059372:Nucleotide Motifs; D056510:Position-Specific Scoring Matrices; D011485:Protein Binding; D021381:Protein Transport; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D016326:Extracellular Matrix Proteins; D055758:SOX9 Transcription Factor