CpG traffic lights are markers of regulatory regions in human genome

BMC Genomics

Abdullah M. Khamis¹  Vladimir B. Bajic¹  Ivan V. Kulakovskiy²  Elizaveta Besedina³  Anna V. Lioznova⁴  Artem V. Artemov⁴  Yulia A. Medvedeva⁴  Vasily Ramensky⁵ 

[1] Computational Bioscience Research Center (CBRC), Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division, King Abdullah University of Science and Technology (KAUST);Engelhardt Institute of Molecular Biology, Russian Academy of Sciences;Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University;Institute of Bioengineering, Research Center of Biotechnology, Russian Academy of Sciences;Moscow Institute of Physics and Technology, Dolgoprudny;

关键词: CpG traffic lights;    DNA methylation;    Transcription regulation;    Enhancers;    CAGE;    Chromatin states;   

DOI  :  10.1186/s12864-018-5387-1

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown