Effects of cytosine methylation on transcription factor binding sites

Handle URI:
http://hdl.handle.net/10754/325243
Title:
Effects of cytosine methylation on transcription factor binding sites
Authors:
Medvedeva, Yulia A; Khamis, Abdullah M. ( 0000-0002-5945-0159 ) ; Kulakovskiy, Ivan V; Ba Alawi, Wail ( 0000-0002-2747-4703 ) ; Bhuyan, Md Shariful I; Kawaji, Hideya; Lassmann, Timo; Harbers, Matthias; Forrest, Alistair RR; Bajic, Vladimir B. ( 0000-0001-5435-4750 )
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. 2013 Medvedeva et al.; licensee BioMed Central Ltd.
KAUST Department:
Computational Bioscience Research Center (CBRC); Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Citation:
Medvedeva YA, Khamis AM, Kulakovskiy IV, Ba-Alawi W, Bhuyan MSI, et al. (2014) Effects of cytosine methylation on transcription factor binding sites. BMC Genomics 15: 119. doi:10.1186/1471-2164-15-119.
Publisher:
Springer Nature
Journal:
BMC Genomics
Issue Date:
26-Mar-2014
DOI:
10.1186/1471-2164-15-119
PubMed ID:
24669864
PubMed Central ID:
PMC3986887
Type:
Article
ISSN:
14712164
Appears in Collections:
Articles; Computational Bioscience Research Center (CBRC); Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorMedvedeva, Yulia Aen
dc.contributor.authorKhamis, Abdullah M.en
dc.contributor.authorKulakovskiy, Ivan Ven
dc.contributor.authorBa Alawi, Wailen
dc.contributor.authorBhuyan, Md Shariful Ien
dc.contributor.authorKawaji, Hideyaen
dc.contributor.authorLassmann, Timoen
dc.contributor.authorHarbers, Matthiasen
dc.contributor.authorForrest, Alistair RRen
dc.contributor.authorBajic, Vladimir B.en
dc.date.accessioned2014-08-27T09:42:01Z-
dc.date.available2014-08-27T09:42:01Z-
dc.date.issued2014-03-26en
dc.identifier.citationMedvedeva YA, Khamis AM, Kulakovskiy IV, Ba-Alawi W, Bhuyan MSI, et al. (2014) Effects of cytosine methylation on transcription factor binding sites. BMC Genomics 15: 119. doi:10.1186/1471-2164-15-119.en
dc.identifier.issn14712164en
dc.identifier.pmid24669864en
dc.identifier.doi10.1186/1471-2164-15-119en
dc.identifier.urihttp://hdl.handle.net/10754/325243en
dc.description.abstractBackground: 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. 2013 Medvedeva et al.; licensee BioMed Central Ltd.en
dc.language.isoenen
dc.publisherSpringer Natureen
dc.rightsThis 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 credited.en
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en
dc.subjectBioinformaticsen
dc.subjectCAGEen
dc.subjectComputational biologyen
dc.subjectCpG " traffic lights"en
dc.subjectDNA methylationen
dc.subjectRRBSen
dc.subjectTranscription factor binding sitesen
dc.subjectTranscriptional regulationen
dc.subjectcytosineen
dc.subjecttranscription factoren
dc.subjectbinding siteen
dc.subjectcap analysis of gene expressionen
dc.subjectcontrolled studyen
dc.subjectcorrelation analysisen
dc.subjectCpG islanden
dc.subjectdinucleotide repeaten
dc.subjectgene expressionen
dc.subjectgene expression profilingen
dc.subjecthuman cellen
dc.subjectpromoter regionen
dc.subjectregulatory mechanismen
dc.subjecttranscription initiation siteen
dc.subjecttranscription regulationen
dc.titleEffects of cytosine methylation on transcription factor binding sitesen
dc.typeArticleen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.contributor.departmentComputer, Electrical and Mathematical Sciences and Engineering (CEMSE) Divisionen
dc.identifier.journalBMC Genomicsen
dc.identifier.pmcidPMC3986887en
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionLaboratory of Bioinformatics and Systems Biology, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov str. 32, Moscow 119991GSP-1, Russian Federationen
dc.contributor.institutionDepartment of Computational Systems Biology, Vavilov Institute of General Genetics, Russian Academy of Sciences, Gubkina str. 3, Moscow 119991, Russian Federationen
dc.contributor.institutionRIKEN Omics Science Center, Yokohama, Kanagawa 230-0045, Japanen
dc.contributor.institutionRIKEN Center for Life Science Technologies, Division of Genomic Technologies, Yokohama, Kanagawa 230-0045, Japanen
dc.contributor.institutionRIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Saitama 351-0198, Japanen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorMedvedeva, Yuliaen
kaust.authorBhuyan, Sharifulislamen
kaust.authorBajic, Vladimir B.en
kaust.authorKhamis, Abdullah M.en
kaust.authorBa Alawi, Wailen

Related articles on PubMed

This item is licensed under a Creative Commons License
Creative Commons
All Items in KAUST are protected by copyright, with all rights reserved, unless otherwise indicated.