Complex impact of DNA methylation on transcriptional dysregulation across 22 human cancer types.

Abstract:

:Accumulating evidence has demonstrated that transcriptional regulation is affected by DNA methylation. Understanding the perturbation of DNA methylation-mediated regulation between transcriptional factors (TFs) and targets is crucial for human diseases. However, the global landscape of DNA methylation-mediated transcriptional dysregulation (DMTD) across cancers has not been portrayed. Here, we systematically identified DMTD by integrative analysis of transcriptome, methylome and regulatome across 22 human cancer types. Our results revealed that transcriptional regulation was affected by DNA methylation, involving hundreds of methylation-sensitive TFs (MethTFs). In addition, pan-cancer MethTFs, the regulatory activity of which is generally affected by DNA methylation across cancers, exhibit dominant functional characteristics and regulate several cancer hallmarks. Moreover, pan-cancer MethTFs were found to be affected by DNA methylation in a complex pattern. Finally, we investigated the cooperation among MethTFs and identified a network module that consisted of 43 MethTFs with prognostic potential. In summary, we systematically dissected the transcriptional dysregulation mediated by DNA methylation across cancer types, and our results provide a valuable resource for both epigenetic and transcriptional regulation communities.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Wang Z,Yin J,Zhou W,Bai J,Xie Y,Xu K,Zheng X,Xiao J,Zhou L,Qi X,Li Y,Li X,Xu J

doi

10.1093/nar/gkaa041

subject

Has Abstract

pub_date

2020-03-18 00:00:00

pages

2287-2302

issue

5

eissn

0305-1048

issn

1362-4962

pii

5718258

journal_volume

48

pub_type

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