CHD6 eviction of promoter nucleosomes maintains housekeeping transcriptional program in prostate cancer.

IF 6.5 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Molecular Therapy. Nucleic Acids Pub Date : 2024-11-16 eCollection Date: 2024-12-10 DOI:10.1016/j.omtn.2024.102397

Lina Bu, Shaodong Huang, Ziyan Rao, Chenyang Wu, Bryan-Yu Sun, Yanhua Liu, Lin He, Dongyu Zhao

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Abstract

CHD6, a member of the chromodomain helicase DNA-binding protein family, has been implicated in various diseases and tumors. However, its precise binding model of CHD6 on regulatory functional genes remains poorly understood. In this study, we discovered sharp peaks of CHD6, as the first member of CHD family for housekeeping process, binding only to the promoter region of genes in the C4-2 cell line. These genes, with conserved sharp CHD6 peaks across tumor cells, likely represent housekeeping genes ADNP and GOLGA5. Genes with sharp CHD6 peaks exhibit stable and low expression levels, sharing epigenetic features similar to housekeeping genes. Furthermore, this regulatory model also exists in both HEK293 cells and cardiomyocytes. Overall, the results of this study demonstrate that CHD6 binds to the promoter regions of housekeeping genes, regulating their histone modifications, chromatin structure, and gene expression.

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前列腺癌中CHD6启动子核小体的清除维持了内务转录程序。

CHD6是染色体结构域解旋酶dna结合蛋白家族的一员，与多种疾病和肿瘤有关。然而，CHD6与调控功能基因的精确结合模式尚不清楚。在本研究中，我们发现CHD6作为CHD家族的第一个成员，在C4-2细胞系中仅与基因的启动子区域结合，出现尖峰。这些基因在肿瘤细胞中具有保守的尖锐CHD6峰，可能代表家务活基因ADNP和GOLGA5。具有CHD6尖峰的基因表现出稳定和低表达水平，具有与管家基因相似的表观遗传特征。此外，这种调节模式也存在于HEK293细胞和心肌细胞中。总的来说，本研究的结果表明CHD6与管家基因的启动子区域结合，调节其组蛋白修饰、染色质结构和基因表达。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Therapy. Nucleic Acids MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

15.40

自引率

1.10%

发文量

336

审稿时长

20 weeks

期刊介绍： Molecular Therapy Nucleic Acids is an international, open-access journal that publishes high-quality research in nucleic-acid-based therapeutics to treat and correct genetic and acquired diseases. It is the official journal of the American Society of Gene & Cell Therapy and is built upon the success of Molecular Therapy. The journal focuses on gene- and oligonucleotide-based therapies and publishes peer-reviewed research, reviews, and commentaries. Its impact factor for 2022 is 8.8. The subject areas covered include the development of therapeutics based on nucleic acids and their derivatives, vector development for RNA-based therapeutics delivery, utilization of gene-modifying agents like Zn finger nucleases and triplex-forming oligonucleotides, pre-clinical target validation, safety and efficacy studies, and clinical trials.