DNA methylation controls unmethylated transcription start sites in the genome in trans
| Autor: | Steffan Christiansen, Anne-Sophie Pepin, Moshe Szyf, Rudy Zhou, Lauren Schmeltzer, Sergey Dymov, Daniel M Sapozhnikov, David Cheishvili, Rebecca Stochinsky |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
DNA (Cytosine-5-)-Methyltransferase 1
Transcriptional Activation 0301 basic medicine EXPRESSION Cancer Research GENES MICRORNAS PROTEINS Ser5 Biology 03 medical and health sciences GLUTAMATE Epigenetics of physical exercise TUMOR Transcription (biology) 5-aza-2 '-deoxycytidine Genetics Humans Gene Silencing Promoter Regions Genetic RNA-Directed DNA Methylation Transcription factor CRISPR/Cas9 Illumina 450k DNA methylation upstream regulators Genome Human DNMT1 WIDE PROLIFERATION Promoter Hep G2 Cells Methylation DNA Methylation NUCLEAR FACTOR 4-ALPHA HNF4A PROSTATE-CANCER 030104 developmental biology Hepatocyte Nuclear Factor 4 Illumina Methylation Assay RNAPII |
| Zdroj: | Cheishvili, D, Christiansen, S, Stochinsky, R, Pepin, A-S, Sapozhnikov, D M, Zhou, R, Schmeltzer, L, Dymov, S & Szyf, M 2017, ' DNA methylation controls unmethylated transcription start sites in the genome in trans ', Epigenomics, vol. 9, no. 5, pp. 611-633 . https://doi.org/10.2217/epi-2016-0141 |
| DOI: | 10.2217/epi-2016-0141 |
| Popis: | Aim: DNA methylation downregulates transcription. However, a large number of genes, which are unmethylated in the promoter region, are inactive. We tested the hypothesis that these genes are regulated by DNA methylation of upstream regulators. Methods: We inhibited DNMT1 with 5-aza-2′-deoxycytidine or depleted it with shRNA to map the transcription initiation positions controlled by DNMT1 using ChIPseq with RNApolIIser5 antibody. Ingenuity pathway analysis identified potential methylated upstream regulators. Their functional role in controlling unmethylated promoters was determined by CRISPR/Cas9 gene editing. Results: We show that a large group of unmethylated promoters is regulated by DNMT1 through DNA methylation dependent silencing of upstream regulators such as transcription factor HNF4A. Conclusion: The landscape of genes regulated by DNA methylation is more wide-ranging than genes downregulated by methylation of their own cis-regulatory sequences; regulation of unmethylated promoters is dependent on the methylation state of upstream trans regulators. |
| Databáze: | OpenAIRE |
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