CHD6 promotes broad nucleosome eviction for transcriptional activation in prostate cancer cells.
CHD6 promotes broad nucleosome eviction for transcriptional activation in prostate cancer cells.
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CHD6促进广泛的核小体驱逐以激活前列腺癌细胞的转录。
DOI：
10.1093/nar/gkac1090
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发表时间：
2022-11-28
影响因子：
14.9
通讯作者：
Chen, Kaifu
中科院分区：
文献类型：
--
作者：
Zhao, Dongyu;Zhang, Min;Huang, Shaodong;Liu, Qi;Zhu, Sen;Li, Yanqiang;Jiang, Weihua;Kiss, Daniel L.;Cao, Qi;Zhang, Lili;Chen, Kaifu
尽管CHD 6是染色体结构域解旋酶DNA结合蛋白家族的成员，但关于CHD 6在染色质重塑或癌症疾病中的确切作用知之甚少。在这里，我们表明，CHD 6结合染色质，以促进广泛的核小体驱逐许多癌症途径的转录激活。通过整合多个患者队列对一千多个前列腺癌数据集进行生物信息学分析，我们发现前列腺癌中CHD 6表达升高，并与预后不良相关。进一步的综合实验表明，CHD 6调节前列腺癌细胞的致癌性和小鼠异种移植模型中的肿瘤发展。针对CHD 6的ChIP-Seq、沿着的MNase-Seq和RNA-Seq揭示了CHD 6结合在染色质上以从启动子和基因体驱逐核小体，用于致癌途径的转录激活。这些结果证明了CHD 6在从染色质中驱逐核小体以转录激活前列腺癌途径中的关键功能。
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.
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影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
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Montgomery SB
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影响因子：
64.8
作者：
Dann GP;Liszczak GP;Bagert JD;Müller MM;Nguyen UTT;Wojcik F;Brown ZZ;Bos J;Panchenko T;Pihl R;Pollock SB;Diehl KL;Allis CD;Muir TW
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Muir TW
影响因子：
14.9
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通讯作者：
Flicek P
影响因子：
8
作者：
Araki, K;Nakajima, Y;Ikeda, MA
通讯作者：
Ikeda, MA
影响因子：
3.8
作者：
Dufresne, Jaimie;Bowden, Pete;Marshall, John G.
通讯作者：
Marshall, John G.