CpG traffic lights are markers of regulatory regions in human genome
Type
DatasetAuthors
Lioznova, Anna V.Khamis, Abdullah M.

Artemov, Artem V.
Besedina, Elizaveta
Ramensky, Vasily
Bajic, Vladimir B.

Kulakovskiy, Ivan V.
Medvedeva, Yulia A.
KAUST Department
Computer Science ProgramComputer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Applied Mathematics and Computational Science Program
Computational Bioscience Research Center (CBRC)
Date
2019Permanent link to this record
http://hdl.handle.net/10754/664422
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Abstract Background DNA methylation is involved in the regulation of gene expression. Although bisulfite-sequencing based methods profile DNA methylation at a single CpG resolution, methylation levels are usually averaged over genomic regions in the downstream bioinformatic analysis. Results We demonstrate that on the genome level a single CpG methylation can serve as a more accurate predictor of gene expression than an average promoter / gene body methylation. We define CpG traffic lights (CpG TL) as CpG dinucleotides with a significant correlation between methylation and expression of a gene nearby. CpG TL are enriched in all regulatory regions. Among all promoters, CpG TL are especially enriched in poised ones, suggesting involvement of DNA methylation in their regulation. Yet, binding of only a handful of transcription factors, such as NRF1, ETS, STAT and IRF-family members, could be regulated by direct methylation of transcription factor binding sites (TFBS) or its close proximity. For the majority of TF, an alternative scenario is more likely: methylation and inactivation of the whole regulatory element indirectly represses functional TF binding with a CpG TL being a reliable marker of such inactivation. Conclusions CpG TL provide a promising insight into mechanisms of enhancer activity and gene regulation linking methylation of single CpG to gene expression. CpG TL methylation can be used as reliable markers of enhancer activity and gene expression in applications, e.g. in clinic where measuring DNA methylation is easier compared to directly measuring gene expression due to more stable nature of DNA.Citation
Lioznova, A. V., Khamis, A. M., Artemov, A. V., Besedina, E., Ramensky, V., Bajic, V. B., Kulakovskiy, I. V., & Medvedeva, Y. A. (2019). CpG traffic lights are markers of regulatory regions in human genome. Figshare. https://doi.org/10.6084/M9.FIGSHARE.C.4387292.V1Publisher
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Lioznova AV, Khamis AM, Artemov AV, Besedina E, Ramensky V, et al. (2019) CpG traffic lights are markers of regulatory regions in human genome. BMC Genomics 20. Available: http://dx.doi.org/10.1186/s12864-018-5387-1.. DOI: 10.1186/s12864-018-5387-1 HANDLE: 10754/631008
ae974a485f413a2113503eed53cd6c53
10.6084/m9.figshare.c.4387292.v1