Genome-wide conserved consensus transcription factor binding motifs are hyper-methylated

  • Choy M
  • Movassagh M
  • Goh H
 et al. 
  • 130

    Readers

    Mendeley users who have this article in their library.
  • 59

    Citations

    Citations of this article.

Abstract

BACKGROUND DNA methylation can regulate gene expression by modulating the interaction between DNA and proteins or protein complexes. Conserved consensus motifs exist across the human genome ("predicted transcription factor binding sites": "predicted TFBS") but the large majority of these are proven by chromatin immunoprecipitation and high throughput sequencing (ChIP-seq) not to be biological transcription factor binding sites ("empirical TFBS"). We hypothesize that DNA methylation at conserved consensus motifs prevents promiscuous or disorderly transcription factor binding. RESULTS Using genome-wide methylation maps of the human heart and sperm, we found that all conserved consensus motifs as well as the subset of those that reside outside CpG islands have an aggregate profile of hyper-methylation. In contrast, empirical TFBS with conserved consensus motifs have a profile of hypo-methylation. 40% of empirical TFBS with conserved consensus motifs resided in CpG islands whereas only 7% of all conserved consensus motifs were in CpG islands. Finally we further identified a minority subset of TF whose profiles are either hypo-methylated or neutral at their respective conserved consensus motifs implicating that these TF may be responsible for establishing or maintaining an un-methylated DNA state, or whose binding is not regulated by DNA methylation. CONCLUSIONS Our analysis supports the hypothesis that at least for a subset of TF, empirical binding to conserved consensus motifs genome-wide may be controlled by DNA methylation.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Get full text

Authors

  • Mun Kit Choy

  • Mehregan Movassagh

  • Hock Guan Goh

  • Martin R. Bennett

  • Thomas A. Down

  • Roger S.Y. Foo

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free