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: Zhongcheng Shi, Chi-I Chiang, Paul Labhart, Yanling Zhao, Jianhua Yang, Toni-Ann Mistretta, Susan J Henning, Sankar N Maity, Yuko Mori-Akiyama
• Journal: Nucleic acids research (Nucleic Acids Res) Vol. 43 Issue 13 Pg. 6257-69 (Jul 27 2015) ISSN: 1362-4962 [Electronic] England
• PMID: 26040697 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Chemical References

• CCAAT-Binding Factor
• NFYA protein, human
• SOX9 Transcription Factor
• SOX9 protein, human

Topics

• Binding Sites
• CCAAT-Binding Factor (metabolism)
• Cell Line, Tumor
• Colorectal Neoplasms (genetics, metabolism)
• Gene Expression Regulation, Neoplastic
• Genome, Human
• Humans
• Promoter Regions, Genetic
• SOX9 Transcription Factor (metabolism, physiology)
• Transcriptional Activation