Effects of cytosine methylation on transcription factor binding sites

BMC Genomics

Vladimir B Bajic²  Alistair RR Forrest⁵  Matthias Harbers⁴  Timo Lassmann⁵  Hideya Kawaji³  Md Shariful I Bhuyan²  Wail Ba-Alawi²  Ivan V Kulakovskiy¹  Abdullah M Khamis²  Yulia A Medvedeva² 

[1] Department of Computational Systems Biology, Vavilov Institute of General Genetics, Russian Academy of Sciences, Gubkina str. 3, Moscow 119991, Russia;Computational Bioscience Research Center, Computer, Electrical and Mathematical Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia;RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Saitama 351-0198, Japan;RIKEN Omics Science Center, Yokohama, Kanagawa 230-0045, Japan;RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Yokohama, Kanagawa 230-0045, Japan

关键词: Computational biology;    Bioinformatics;    CpG “traffic lights”;    RRBS;    CAGE;    Transcriptional regulation;    Transcription factor binding sites;    DNA methylation;   

Others  :  1217633
DOI  :  10.1186/1471-2164-15-119

 received in 2013-04-16, accepted in 2013-08-16,  发布年份 2014

【 摘 要 】

Background

DNA methylation in promoters is closely linked to downstream gene repression. However, whether DNA methylation is a cause or a consequence of gene repression remains an open question. If it is a cause, then DNA methylation may affect the affinity of transcription factors (TFs) for their binding sites (TFBSs). If it is a consequence, then gene repression caused by chromatin modification may be stabilized by DNA methylation. Until now, these two possibilities have been supported only by non-systematic evidence and they have not been tested on a wide range of TFs. An average promoter methylation is usually used in studies, whereas recent results suggested that methylation of individual cytosines can also be important.

Results

We found that the methylation profiles of 16.6% of cytosines and the expression profiles of neighboring transcriptional start sites (TSSs) were significantly negatively correlated. We called the CpGs corresponding to such cytosines “traffic lights”. We observed a strong selection against CpG “traffic lights” within TFBSs. The negative selection was stronger for transcriptional repressors as compared with transcriptional activators or multifunctional TFs as well as for core TFBS positions as compared with flanking TFBS positions.

Conclusions

Our results indicate that direct and selective methylation of certain TFBS that prevents TF binding is restricted to special cases and cannot be considered as a general regulatory mechanism of transcription.

【 授权许可】

   
2013 Medvedeva et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

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