CpG traffic lights are markers of regulatory regions in humans

Handle URI:
http://hdl.handle.net/10754/625213
Title:
CpG traffic lights are markers of regulatory regions in humans
Authors:
Khamis, Abdullah M. ( 0000-0002-5945-0159 ) ; Lioznova, Anna V. ( 0000-0001-8094-0083 ) ; Artemov, Artem V.; Ramensky, Vasily; Bajic, Vladimir B. ( 0000-0001-5435-4750 ) ; Medvedeva, Yulia A.
Abstract:
DNA methylation is involved in regulation of gene expression. Although modern methods profile DNA methylation at single CpG sites, methylation levels are usually averaged over genomic regions in the downstream analyses. In this study we demonstrate that single CpG methylation can serve as a more accurate predictor of gene expression compared to average promoter / gene body methylation. CpG positions with significant correlation between methylation and expression of a gene nearby (named CpG traffic lights) are evolutionary conserved and enriched for exact TSS positions and active enhancers. Among all promoter types, CpG traffic lights are especially enriched in poised promoters. Genes that harbor CpG traffic lights are associated with development and signal transduction. Methylation levels of individual CpG traffic lights vary between cell types dramatically with the increased frequency of intermediate methylation levels, indicating cell population heterogeneity in CpG methylation levels. Being in line with the concept of the inherited stochastic epigenetic variation, methylation of such CpG positions might contribute to transcriptional regulation. Alternatively, one can hypothesize that traffic lights are markers of absent gene expression resulting from inactivation of their regulatory elements. The CpG traffic lights provide a promising insight into mechanisms of enhancer activity and gene regulation linking methylation of single CpG to expression.
KAUST Department:
Computational Bioscience Research Center (CBRC); Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Citation:
Khamis AM, Lioznova AV, Artemov AV, Ramensky V, Bajic VB, et al. (2016) CpG traffic lights are markers of regulatory regions in humans. Available: http://dx.doi.org/10.1101/095968.
Publisher:
Cold Spring Harbor Laboratory Press
Issue Date:
29-Dec-2016
DOI:
10.1101/095968
Type:
Working Paper
Sponsors:
This work was supported by RFBR grant 14-04-00180 to YAM. VBB is supported by the base research fund of the King Abdullah University of Science and Technology (KAUST).
Additional Links:
http://www.biorxiv.org/content/early/2017/03/17/095968
Appears in Collections:
Other/General Submission; Computational Bioscience Research Center (CBRC); Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorKhamis, Abdullah M.en
dc.contributor.authorLioznova, Anna V.en
dc.contributor.authorArtemov, Artem V.en
dc.contributor.authorRamensky, Vasilyen
dc.contributor.authorBajic, Vladimir B.en
dc.contributor.authorMedvedeva, Yulia A.en
dc.date.accessioned2017-07-19T10:45:00Z-
dc.date.available2017-07-19T10:45:00Z-
dc.date.issued2016-12-29en
dc.identifier.citationKhamis AM, Lioznova AV, Artemov AV, Ramensky V, Bajic VB, et al. (2016) CpG traffic lights are markers of regulatory regions in humans. Available: http://dx.doi.org/10.1101/095968.en
dc.identifier.doi10.1101/095968en
dc.identifier.urihttp://hdl.handle.net/10754/625213-
dc.description.abstractDNA methylation is involved in regulation of gene expression. Although modern methods profile DNA methylation at single CpG sites, methylation levels are usually averaged over genomic regions in the downstream analyses. In this study we demonstrate that single CpG methylation can serve as a more accurate predictor of gene expression compared to average promoter / gene body methylation. CpG positions with significant correlation between methylation and expression of a gene nearby (named CpG traffic lights) are evolutionary conserved and enriched for exact TSS positions and active enhancers. Among all promoter types, CpG traffic lights are especially enriched in poised promoters. Genes that harbor CpG traffic lights are associated with development and signal transduction. Methylation levels of individual CpG traffic lights vary between cell types dramatically with the increased frequency of intermediate methylation levels, indicating cell population heterogeneity in CpG methylation levels. Being in line with the concept of the inherited stochastic epigenetic variation, methylation of such CpG positions might contribute to transcriptional regulation. Alternatively, one can hypothesize that traffic lights are markers of absent gene expression resulting from inactivation of their regulatory elements. The CpG traffic lights provide a promising insight into mechanisms of enhancer activity and gene regulation linking methylation of single CpG to expression.en
dc.description.sponsorshipThis work was supported by RFBR grant 14-04-00180 to YAM. VBB is supported by the base research fund of the King Abdullah University of Science and Technology (KAUST).en
dc.publisherCold Spring Harbor Laboratory Pressen
dc.relation.urlhttp://www.biorxiv.org/content/early/2017/03/17/095968en
dc.rightsIt is made available under a CC-BY-NC-ND 4.0 International license.en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectRegulation of transcriptionen
dc.subjectDNA methylationen
dc.subjectenhancersen
dc.subjectCAGEen
dc.subjectchromatin statesen
dc.subjectCpG traffic lightsen
dc.titleCpG traffic lights are markers of regulatory regions in humansen
dc.typeWorking Paperen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.contributor.departmentComputer, Electrical and Mathematical Sciences and Engineering (CEMSE) Divisionen
dc.eprint.versionPre-printen
dc.contributor.institutionInstitute of Bioengineering, Research Center of Biotechnology, Russian Academy of Sciences, Moscow 119071, Russian Federationen
dc.contributor.institutionInstitute for Information Transmission Problems (Kharkevich Institute), Russian Academy of Sciences, Moscow 127051, Russian Federationen
dc.contributor.institutionFaculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 119991, Russian Federationen
dc.contributor.institutionImmanuel Kant Baltic Federal University, Kaliningrad 236041, Russian Federationen
dc.contributor.institutionMoscow Institute of Physics and Technology, Dolgoprudny, Moscow Region 141701, Russian Federationen
dc.contributor.institutionCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, California 90095, USAen
dc.contributor.institutionVavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119991, Russian Federationen
kaust.authorKhamis, Abdullah M.en
kaust.authorBajic, Vladimir B.en
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