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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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


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