染色质调节因子的协同相互作用图谱揭示了它们在五种癌细胞系中的表观遗传调控机制。

The synergistic interaction landscape of chromatin regulators reveals their epigenetic regulation mechanisms across five cancer cell lines.

作者信息

Cao Meng, Wang Liqiang, Xu Dahua, Bi Xiaoman, Guo Shengnan, Xu Zhizhou, Chen Liyang, Zheng Dehua, Li Peihu, Xu Jiankai, Zheng Shaojiang, Wang Hong, Wang Bo, Lu Jianping, Li Kongning

机构信息

Key Laboratory of Tropical Translational Medicine of Ministry of Education, College of Biomedical Information and Engineering, Hainan General Hospital and Hainan Affiliated Hospital, Hainan Medical University, Haikou, China.

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.

出版信息

Comput Struct Biotechnol J. 2022 Sep 12;20:5028-5039. doi: 10.1016/j.csbj.2022.09.008. eCollection 2022.

DOI:10.1016/j.csbj.2022.09.008

PMID:36187922

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9483781/

Abstract

Chromatin regulators (CRs) regulate the gene transcription process through combinatorial patterns, which currently remain obscure for pan-cancer. This study identified the interaction of CRs and constructed CR-CR interaction networks across five tumor cell lines. The global interaction analysis revealed that CRs tend to function in synergistically. In addition, common and specific CRs in interaction networks were identified, and the epigenetic processes of these CRs in regulating gene transcription were analyzed. Common CRs have conserved binding sites but cooperate with different partners in multiple tumor cell lines. They also participate in gene transcription regulation, through mediation of different histone modifications (HMs). Specific CRs, ATF2 and PRDM10 were found to distinguish liver cancer samples with different prognosis. PRDM10 participates in gene transcription regulation, by exertion of influence on the DNA methylation level of liver cancer. Through analysis of the edges in the CR-CR interaction networks, it was found EP300-TAF1 has genome-wide distinct signaling patterns, which exhibit different effects on downstream targets. This analysis provides novel insights for the understanding of synergistic mechanism of CRs function, as controllers of gene transcription across cancer types.

摘要

染色质调节因子（CRs）通过组合模式调控基因转录过程，目前在泛癌研究中仍不清楚。本研究确定了CRs之间的相互作用，并构建了跨越五种肿瘤细胞系的CR-CR相互作用网络。全局相互作用分析表明，CRs倾向于协同发挥作用。此外，还确定了相互作用网络中的常见和特异性CRs，并分析了这些CRs在调控基因转录中的表观遗传过程。常见的CRs具有保守的结合位点，但在多种肿瘤细胞系中与不同的伙伴合作。它们还通过介导不同的组蛋白修饰（HMs）参与基因转录调控。发现特异性CRs，即ATF2和PRDM10，可区分不同预后的肝癌样本。PRDM10通过影响肝癌的DNA甲基化水平参与基因转录调控。通过分析CR-CR相互作用网络中的边，发现EP300-TAF1具有全基因组范围内独特的信号模式，对下游靶点表现出不同的影响。该分析为理解CRs作为跨癌症类型基因转录调控因子的协同作用机制提供了新的见解。