Context-specific role of SOX9 in NF-Y mediated gene regulation in colorectal cancer cells
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 rece...
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Oxford University Press
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4513854/ |
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pubmed-45138542015-07-27 Context-specific role of SOX9 in NF-Y mediated gene regulation in colorectal cancer cells Shi, Zhongcheng Chiang, Chi-I Labhart, Paul Zhao, Yanling Yang, Jianhua Mistretta, Toni-Ann Henning, Susan J. Maity, Sankar N. Mori-Akiyama, Yuko Gene regulation, Chromatin and Epigenetics 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. Oxford University Press 2015-07-27 2015-06-03 /pmc/articles/PMC4513854/ /pubmed/26040697 http://dx.doi.org/10.1093/nar/gkv568 Text en © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Shi, Zhongcheng Chiang, Chi-I Labhart, Paul Zhao, Yanling Yang, Jianhua Mistretta, Toni-Ann Henning, Susan J. Maity, Sankar N. Mori-Akiyama, Yuko |
| spellingShingle |
Shi, Zhongcheng Chiang, Chi-I Labhart, Paul Zhao, Yanling Yang, Jianhua Mistretta, Toni-Ann Henning, Susan J. Maity, Sankar N. Mori-Akiyama, Yuko Context-specific role of SOX9 in NF-Y mediated gene regulation in colorectal cancer cells |
| author_facet |
Shi, Zhongcheng Chiang, Chi-I Labhart, Paul Zhao, Yanling Yang, Jianhua Mistretta, Toni-Ann Henning, Susan J. Maity, Sankar N. Mori-Akiyama, Yuko |
| author_sort |
Shi, Zhongcheng |
| title |
Context-specific role of SOX9 in NF-Y mediated gene regulation in colorectal cancer cells |
| title_short |
Context-specific role of SOX9 in NF-Y mediated gene regulation in colorectal cancer cells |
| title_full |
Context-specific role of SOX9 in NF-Y mediated gene regulation in colorectal cancer cells |
| title_fullStr |
Context-specific role of SOX9 in NF-Y mediated gene regulation in colorectal cancer cells |
| title_full_unstemmed |
Context-specific role of SOX9 in NF-Y mediated gene regulation in colorectal cancer cells |
| title_sort |
context-specific role of sox9 in nf-y mediated gene regulation in colorectal cancer cells |
| description |
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. |
| publisher |
Oxford University Press |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4513854/ |
| _version_ |
1613251799642275840 |