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

BMC Genomics

Research Article

Hock-Guan Goh¹  Mun-Kit Choy²  Martin R Bennett²  Roger SY Foo²  Mehregan Movassagh²  Thomas A Down³ 

[1] Department of Computer and Communication Technology, Faculty of Information, Communication and Technology, University of Tunku Abdul Rahman, Perak, Malaysia;Department of Medicine, University of Cambridge, ACCI Building Level 6, CB2 0QQ, Cambridge, UK;The Gurdon Institute and Department of Genetics, University of Cambridge, CB2 1QN, Cambridge, UK;

关键词: Transcription Factor Binding Site;    Methylation Profile;    UCSC Genome Browser;    Transcription Factor Complex;    Transcription Factor Binding Motif;   

DOI  :  10.1186/1471-2164-11-519

 received in 2010-05-12, accepted in 2010-09-27,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundDNA 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.ResultsUsing 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.ConclusionsOur 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.

【 授权许可】

Unknown   
© Choy et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.