title: Context-specific role of SOX9 in NF-Y mediated gene regulation in colorectal cancer cells.
abstract: Roles for SOX9 have been extensively studied in development and particular emphasis has been placed on SOX9 roles in cell lineage determination in a number of discrete tissues. Aberrant expression of SOX9 in many cancers, including colorectal cancer, suggests roles in these diseases as well and recent studies have suggested tissue- and context-specific roles of SOX9. Our genome wide approach by chromatin immunoprecipitation sequencing (ChIP-seq) in human colorectal cancer cells identified a number of physiological targets of SOX9, including ubiquitously expressed cell cycle regulatory genes, such as CCNB1 and CCNB2, CDK1, and TOP2A. These novel high affinity-SOX9 binding peaks precisely overlapped with binding sites for histone-fold NF-Y transcription factor. Furthermore, our data showed that SOX9 is recruited by NF-Y to these promoters of cell cycle regulatory genes and that SOX9 is critical for the full function of NF-Y in activation of the cell cycle genes. Mutagenesis analysis and in vitro binding assays provided additional evidence to show that SOX9 affinity is through NF-Y and that SOX9 DNA binding domain is not necessary for SOX9 affinity to those target genes. Collectively, our results reveal possibly a context-dependent, non-classical regulatory role for SOX9.
authors.affiliation: Department of Pathology & Immunology, Baylor College of Medicine, Texas Children's Hospital, 1102 Bates Street, Suite FC 830.27, Houston, TX 77030-2399, USA.
authors.forename: Zhongcheng
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Department of Pathology & Immunology, Baylor College of Medicine, Texas Children's Hospital, 1102 Bates Street, Suite FC 830.27, Houston, TX 77030-2399, USA.
authors.forename: Chi-I
authors.initials: CI
authors.lastname: Chiang
authors.affiliation: Active Motif, 1914 Palomar Oaks Way, Suite 150, Carlsbad, CA 92008, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Labhart
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Texas Children's Cancer Center, Houston, TX 77030-2399, USA.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Texas Children's Cancer Center, Houston, TX 77030-2399, USA.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Pathology & Immunology, Baylor College of Medicine, Texas Children's Hospital, 1102 Bates Street, Suite FC 830.27, Houston, TX 77030-2399, USA.
authors.forename: Toni-Ann
authors.initials: TA
authors.lastname: Mistretta
authors.affiliation: Department of Medicine, Cell Biology & Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7032, USA.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Henning
authors.affiliation: Department of Genitourinary Medical Oncology-Research, Division of Cancer Medicine, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Sankar N
authors.initials: SN
authors.lastname: Maity
authors.affiliation: Department of Pathology & Immunology, Baylor College of Medicine, Texas Children's Hospital, 1102 Bates Street, Suite FC 830.27, Houston, TX 77030-2399, USA moriakiy@bcm.edu.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Mori-Akiyama
mesh_terms: D001665:Binding Sites; D023081:CCAAT-Binding Factor / Q000378:metabolism*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D011401:Promoter Regions, Genetic; D055758:SOX9 Transcription Factor / Q000378:metabolism* / Q000502:physiology; D015533:Transcriptional Activation
chemical_list: D023081:CCAAT-Binding Factor; C492061:NFYA protein, human; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human