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Nucleic Acids Res. 2015 Jul 27;43(13):6257-69. doi: 10.1093/nar/gkv568. Epub 2015 Jun 3.

Context-specific role of SOX9 in NF-Y mediated gene regulation in colorectal cancer cells.

Author information

1
Department of Pathology & Immunology, Baylor College of Medicine, Texas Children's Hospital, 1102 Bates Street, Suite FC 830.27, Houston, TX 77030-2399, USA.
2
Active Motif, 1914 Palomar Oaks Way, Suite 150, Carlsbad, CA 92008, USA.
3
Department of Pediatrics, Baylor College of Medicine, Texas Children's Cancer Center, Houston, TX 77030-2399, USA.
4
Department of Medicine, Cell Biology & Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7032, USA.
5
Department of Genitourinary Medical Oncology-Research, Division of Cancer Medicine, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
6
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.

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.

PMID:
26040697
PMCID:
PMC4513854
DOI:
10.1093/nar/gkv568
[Indexed for MEDLINE]
Free PMC Article

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