CHD6 promotes broad nucleosome eviction for transcriptional activation in prostate cancer cells
Abstract
Despite being a member of the chromodomain helicase DNA-binding protein family, little is known about the exact role of CHD6 in chromatin remodeling or cancer disease. Here we show that CHD6 binds to chromatin to promote broad nucleosome eviction for transcriptional activation of many cancer pathways. By integrating multiple patient cohorts for bioinformatics analysis of over a thousand prostate cancer datasets, we found CHD6 expression elevated in prostate cancer and associated with poor prognosis. Further comprehensive experiments demonstrated that CHD6 regulates oncogenicity of prostate cancer cells and tumor development in a murine xenograft model. ChIP-Seq for CHD6, along with MNase-Seq and RNA-Seq, revealed that CHD6 binds on chromatin to evict nucleosomes from promoters and gene bodies for transcriptional activation of oncogenic pathways. These results demonstrated a key function of CHD6 in evicting nucleosomes from chromatin for transcriptional activation of prostate cancer pathways.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 21, 2022
- Source ID
- 10.1093/nar/gkac1090
Entities
People
- Daniel L Kiss
- Dongyu Zhao
- Kaifu Chen
- Lili Zhang
- Min Zhang
- Qi Cao
- Qi Liu
- Sen Zhu
- Shaodong Huang
- Weihua Jiang
- Yanqiang Li
Organizations
- Boston Children's Hospital
- Harvard Medical School
- Harvard University
- Houston Methodist Hospital
- National Institutes of Health
- Northwestern University
- Peking University Health Science Center
- Robert H. Lurie Comprehensive Cancer Center
- United States Department of Defense