title: Identification of SOX9 interaction sites in the genome of chondrocytes.
abstract: BACKGROUND
  Our previous work has provided strong evidence that the transcription factor SOX9 is completely needed for chondrogenic differentiation and cartilage formation acting as a "master switch" in this differentiation. Heterozygous mutations in SOX9 cause campomelic dysplasia, a severe skeletal dysmorphology syndrome in humans characterized by a generalized hypoplasia of endochondral bones. To obtain insights into the logic used by SOX9 to control a network of target genes in chondrocytes, we performed a ChIP-on-chip experiment using SOX9 antibodies.
  
  
  RESULTS
  The ChIP DNA was hybridized to a microarray, which covered 80 genes, many of which are involved in chondrocyte differentiation. Hybridization peaks were detected in a series of cartilage extracellular matrix (ECM) genes including Col2a1, Col11a2, Aggrecan and Cdrap as well as in genes for specific transcription factors and signaling molecules. Our results also showed SOX9 interaction sites in genes that code for proteins that enhance the transcriptional activity of SOX9. Interestingly, a strong SOX9 signal was also observed in genes such as Col1a1 and Osx, whose expression is strongly down regulated in chondrocytes but is high in osteoblasts. In the Col2a1 gene, in addition to an interaction site on a previously identified enhancer in intron 1, another strong interaction site was seen in intron 6. This site is free of nucleosomes specifically in chondrocytes suggesting an important role of this site on Col2a1 transcription regulation by SOX9.
  
  
  CONCLUSIONS
  Our results provide a broad understanding of the strategies used by a "master" transcription factor of differentiation in control of the genetic program of chondrocytes.
authors.affiliation: Department of Genetics, M.D. Anderson Cancer Center, The University of Texas, Houston, Texas, United States of America.
authors.forename: Chun-do
authors.initials: CD
authors.lastname: Oh
authors.forename: Sankar N
authors.initials: SN
authors.lastname: Maity
authors.forename: Jing-Fang
authors.initials: JF
authors.lastname: Lu
authors.forename: Jiexin
authors.initials: J
authors.lastname: Zhang
authors.forename: Shoudan
authors.initials: S
authors.lastname: Liang
authors.forename: Francoise
authors.initials: F
authors.lastname: Coustry
authors.forename: Benoit
authors.initials: B
authors.lastname: de Crombrugghe
authors.forename: Hideyo
authors.initials: H
authors.lastname: Yasuda
mesh_terms: D000818:Animals; D001665:Binding Sites; D002356:Cartilage / Q000166:cytology; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D019902:Chondrocytes / Q000166:cytology*; D024043:Collagen Type II / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D016678:Genome; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D055758:SOX9 Transcription Factor / Q000235:genetics* / Q000378:metabolism
chemical_list: C511513:COL2A1 protein, rat; D024043:Collagen Type II; D016326:Extracellular Matrix Proteins; D055758:SOX9 Transcription Factor
references.citation: J Bone Miner Res. 1999 May;14(5):757-63
references.pmid: 10320524
references.citation: J Histochem Cytochem. 1999 Nov;47(11):1351-6
references.pmid: 10544208
references.citation: Cancer Epidemiol Biomarkers Prev. 2007 Aug;16(8):1667-74
references.pmid: 17684144
references.citation: J Biol Chem. 2004 Dec 17;279(51):53848-56
references.pmid: 15456762
references.citation: Development. 1998 Oct;125(19):3831-42
references.pmid: 9729491
references.citation: Cell Tissue Res. 2001 Oct;306(1):107-16
references.pmid: 11683172
references.citation: Proc Natl Acad Sci U S A. 2006 Jan 10;103(2):365-70
references.pmid: 16387856
references.citation: Nucleic Acids Res. 2008 May;36(9):3011-24
references.pmid: 18390577
references.citation: Biochem Biophys Res Commun. 2005 Aug 12;333(4):1300-8
references.pmid: 15979579
references.citation: Development. 1998 Dec;125(24):4977-88
references.pmid: 9811582
references.citation: Curr Biol. 2004 Jul 27;14(14):R546-51
references.pmid: 15268870
references.citation: Osteoarthritis Cartilage. 2003 Jan;11(1):36-43
references.pmid: 12505485
references.citation: Dev Biol. 2001 Apr 15;232(2):372-87
references.pmid: 11401399
references.citation: Biochem Biophys Res Commun. 1986 Dec 30;141(3):904-11
references.pmid: 3028392
references.citation: J Cell Sci. 1995 Dec;108 ( Pt 12):3677-84
references.pmid: 8719874
references.citation: Mol Cell Biol. 2000 Jun;20(11):4149-58
references.pmid: 10805756
references.citation: J Biol Chem. 1991 Dec 5;266(34):23274-81
references.pmid: 1744124
references.citation: Science. 1988 Oct 21;242(4877):405-11
references.pmid: 3175662
references.citation: Cell. 1992 Oct 30;71(3):399-410
references.pmid: 1339316
references.citation: Genes Dev. 2003 Jul 1;17(13):1677-89
references.pmid: 12842915
references.citation: J Biol Chem. 2005 Sep 30;280(39):33132-40
references.pmid: 16043491
references.citation: J Biol Chem. 1995 Nov 17;270(46):27711-9
references.pmid: 7499238
references.citation: Genesis. 2002 Feb;32(2):121-3
references.pmid: 11857796
references.citation: Front Biosci. 1999 Oct 15;4:D694-703
references.pmid: 10525480
references.citation: Nat Neurosci. 2003 Jan;6(1):21-7
references.pmid: 12469128
references.citation: Curr Biol. 2005 Aug 9;15(15):1340-51
references.pmid: 16085486
references.citation: Genes Dev. 2002 Nov 1;16(21):2813-28
references.pmid: 12414734
references.citation: Arthritis Res Ther. 2006;8(2):106
references.pmid: 16563183
references.citation: Genes Dev. 2004 Oct 1;18(19):2404-17
references.pmid: 15371327
references.citation: J Biol Chem. 2001 Feb 16;276(7):4879-85
references.pmid: 11098049
references.citation: Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6698-703
references.pmid: 11371614
references.citation: Development. 2003 Jun;130(12):2779-91
references.pmid: 12736220
references.citation: Front Biosci. 2008 Jan 01;13:898-903
references.pmid: 17981598
references.citation: Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2414-9
references.pmid: 15699338
references.citation: J Biol Chem. 2000 Feb 4;275(5):3687-92
references.pmid: 10652367
references.citation: Development. 2004 Mar;131(6):1309-18
references.pmid: 14973297
references.citation: Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14665-70
references.pmid: 16203988
references.citation: Cell. 1989 Feb 24;56(4):607-17
references.pmid: 2537150
references.citation: Nat Genet. 2007 Oct;39(10):1235-44
references.pmid: 17873876
references.citation: J Cell Physiol. 2007 Oct;213(1):1-8
references.pmid: 17492773
references.citation: Mol Cell Biol. 1996 Aug;16(8):4512-23
references.pmid: 8754852
references.citation: Nature. 2008 Jun 12;453(7197):930-4
references.pmid: 18454134
references.citation: J Biol Chem. 2002 Nov 1;277(44):42171-7
references.pmid: 12194984
references.citation: Science. 2000 Dec 22;290(5500):2306-9
references.pmid: 11125145
references.citation: Mol Cell Biol. 2007 Sep;27(18):6497-505
references.pmid: 17620412
references.citation: Proc Natl Acad Sci U S A. 2001 Jan 2;98(1):160-5
references.pmid: 11120880
references.citation: Mol Cell Biol. 1997 Apr;17(4):2336-46
references.pmid: 9121483
references.citation: Arthritis Res Ther. 2006;8(4):R124
references.pmid: 16859525
references.citation: Cell. 2002 Jan 11;108(1):17-29
references.pmid: 11792318
references.citation: Bone. 2004 Jan;34(1):26-36
references.pmid: 14751560
references.citation: Matrix Biol. 1994 Aug;14(4):329-35
references.pmid: 7827756
references.citation: Ann Rheum Dis. 1988 Aug;47(8):684-91
references.pmid: 3415368
references.citation: Genes Dev. 1999 Aug 15;13(16):2072-86
references.pmid: 10465785
references.citation: Gastroenterology. 2007 Aug;133(2):539-46
references.pmid: 17681175
references.citation: J Biol Chem. 1998 Jun 12;273(24):14998-5006
references.pmid: 9614107
references.citation: Arthritis Rheum. 2002 Apr;46(4):961-7
references.pmid: 11953973
references.citation: Development. 1998 Nov;125(21):4175-84
references.pmid: 9753672
references.citation: J Biol Chem. 1995 Nov 17;270(46):27734-41
references.pmid: 7499241
references.citation: Nat Genet. 2006 Oct;38(10):1210-5
references.pmid: 16964265
references.citation: J Biol Chem. 2000 Apr 14;275(15):10738-44
references.pmid: 10753864
references.citation: Nature. 2009 Mar 19;458(7236):362-6
references.pmid: 19092803
references.citation: J Biol Chem. 1997 Jul 25;272(30):18709-17
references.pmid: 9228042
references.citation: Development. 2004 May;131(9):1891-901
references.pmid: 15056615
references.citation: Biochem J. 1998 Feb 15;330 ( Pt 1):549-57
references.pmid: 9461555
references.citation: Bone. 1993 May-Jun;14(3):341-5
references.pmid: 8395866
references.citation: J Biol Chem. 2005 Apr 1;280(13):12758-65
references.pmid: 15695815
references.citation: Dev Biol. 1999 May 15;209(2):239-53
references.pmid: 10328918
references.citation: Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1113-8
references.pmid: 10655493
references.citation: Hum Mol Genet. 2003 Jul 15;12(14):1755-65
references.pmid: 12837698
references.citation: J Biol Chem. 2004 Feb 13;279(7):6152-62
references.pmid: 14630908
references.citation: Nature. 1994 Dec 8;372(6506):525-30
references.pmid: 7990924
references.citation: Cell. 2009 May 1;137(3):445-58
references.pmid: 19410542
references.citation: Science. 1999 Jul 16;285(5426):409-12
references.pmid: 10411504
references.citation: Nature. 2006 Aug 17;442(7104):772-8
references.pmid: 16862119