Effects of cytosine methylation on transcription factor binding sites

Medvedeva, Yulia A., Khamis, Abdullah M., Kulakovskiy, Ivan V., Ba-Alawi, Wail, Bhuyan, Md Shariful I., Kawaji, Hideya, Lassmann, Timo, Harbers, Matthias, Forrest, Alistair R. R., Bajic, Vladimir B. and The FANTOM Consortium (2014) Effects of cytosine methylation on transcription factor binding sites. BMC Genomics, 15 119: 1-12. doi:10.1186/1471-2164-15-119

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Author Medvedeva, Yulia A.
Khamis, Abdullah M.
Kulakovskiy, Ivan V.
Ba-Alawi, Wail
Bhuyan, Md Shariful I.
Kawaji, Hideya
Lassmann, Timo
Harbers, Matthias
Forrest, Alistair R. R.
Bajic, Vladimir B.
The FANTOM Consortium
Title Effects of cytosine methylation on transcription factor binding sites
Journal name BMC Genomics   Check publisher's open access policy
ISSN 1471-2164
Publication date 2014-03-26
Sub-type Article (original research)
DOI 10.1186/1471-2164-15-119
Open Access Status DOI
Volume 15
Issue 119
Start page 1
End page 12
Total pages 12
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Formatted abstract
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.
Keyword DNA methylation
Transcription factor binding sites
Transcriptional regulation
CpG "traffic lights"
Computational biology
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
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Citation counts: TR Web of Science Citation Count  Cited 54 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 27 Jun 2014, 01:22:04 EST by Cathy Fouhy on behalf of Aust Institute for Bioengineering & Nanotechnology