Multi-omic analysis suggests tumor suppressor genes evolved specific promoter features to optimize cancer resistance

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Dan Huang
  • Xiansong Wang
  • Yingzhi Liu
  • Ziheng Huang
  • Xiaoxu Hu
  • Wei Hu
  • Qing Li
  • Hung Chan
  • Yidan Zou
  • Idy H.T. Ho
  • Yan Wang
  • Alfred S.L. Cheng
  • Wei Kang
  • Ka F. To
  • Maggie H.T. Wang
  • Sunny H. Wong
  • Jun Yu
  • Tony Gin
  • Zheng Li
  • Jianxiong Shen
  • Lin Zhang
  • Matthew T.V. Chan
  • Xiaodong Liu
  • William K.K. Wu

Related Research Unit(s)

Detail(s)

Original languageEnglish
Pages (from-to)1–12
Journal / PublicationBriefings in Bioinformatics
Volume22
Issue number5
Online published30 Mar 2021
Publication statusPublished - Sep 2021

Abstract

Tumor suppressor genes (TSGs) exhibit distinct evolutionary features. We speculated that TSG promoters could have evolved specific features that facilitate their tumor-suppressing functions. We found that the promoter CpG dinucleotide frequencies of TSGs are significantly higher than that of non-cancer genes across vertebrate genomes, and positively correlated with gene expression across tissue types. The promoter CpG dinucleotide frequencies of all genes gradually increase with gene age, for which young TSGs have been subject to a stronger evolutionary pressure. Transcription-related features, namely chromatin accessibility, methylation and ZNF263-, SP1-, E2F4- and SP2-binding elements, are associated with gene expression. Moreover, higher promoter CpG dinucleotide frequencies and chromatin accessibility are positively associated with the ability of TSGs to resist downregulation during tumorigenesis. These results were successfully validated with independent datasets. In conclusion, TSGs evolved specific promoter features that optimized cancer resistance through achieving high expression in normal tissues and resistance to downregulation during tumorigenesis.

Research Area(s)

  • promoter evolution, pan-cancer, CpG island, chromatin, methylation

Bibliographic Note

Full text of this publication does not contain sufficient affiliation information. With consent from the author(s) concerned, the Research Unit(s) information for this record is based on the existing academic department affiliation of the author(s).

Citation Format(s)

Multi-omic analysis suggests tumor suppressor genes evolved specific promoter features to optimize cancer resistance. / Huang, Dan; Wang, Xiansong; Liu, Yingzhi; Huang, Ziheng; Hu, Xiaoxu; Hu, Wei; Li, Qing; Chan, Hung; Zou, Yidan; Ho, Idy H.T.; Wang, Yan; Cheng, Alfred S.L.; Kang, Wei; To, Ka F.; Wang, Maggie H.T.; Wong, Sunny H.; Yu, Jun; Gin, Tony; Zhang, Qingpeng; Li, Zheng; Shen, Jianxiong; Zhang, Lin; Chan, Matthew T.V.; Liu, Xiaodong; Wu, William K.K.

In: Briefings in Bioinformatics, Vol. 22, No. 5, 09.2021, p. 1–12.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review