| Title | CHD6 promotes broad nucleosome eviction for transcriptional activation in prostate cancer cells |
| Authors | Zhao, Dongyu Zhang, Min Huang, Shaodong Liu, Qi Zhu, Sen Li, Yanqiang Jiang, Weihua Kiss, Daniel L. Cao, Qi Zhang, Lili Chen, Kaifu |
| Affiliation | Peking Univ, Sch Basic Med Sci, Dept Biomed Informat, MOE Key Lab Cardiovasc Sci,Hlth Sci Ctr, Beijing 100191, Peoples R China Harvard Univ, Dana Farber & Harvard Canc Ctr, Prostate Canc Program, Boston, MA 02115 USA Boston Childrens Hosp, Dept Cardiol, Basic & Translat Res Div, Boston, MA 02115 USA Houston Methodist Res Inst, Dept Cardiovasc Sci, Houston, TX 77030 USA Houston Methodist Res Inst, Ctr Inflammat & Epigenet, Houston, TX 77030 USA Northwestern Univ, Dept Urol, Chicago, IL 60611 USA Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Feinberg Sch Med, Chicago, IL 60611 USA Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA |
| Keywords | CHROMATIN REMODELING ENZYMES INFLUENZA-VIRUS REPLICATION EMERGING ROLES GENOME GENES PROLIFERATION RESISTANCE TRANSLOCATION MECHANISMS REPRESSION |
| Issue Date | Nov-2022 |
| Publisher | NUCLEIC ACIDS RESEARCH |
| 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. |
| URI | http://hdl.handle.net/20.500.11897/660930 |
| ISSN | 0305-1048 |
| DOI | 10.1093/nar/gkac1090 |
| Indexed | SCI(E) |
| Appears in Collections: | 基础医学院 |
