DNA methylation controls unmethylated transcription start sites in the genome in trans
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DNA methylation controls unmethylated transcription start sites in the genome in trans. / Cheishvili, David; Christiansen, Steffan; Stochinsky, Rebecca; Pepin, Anne-Sophie; Sapozhnikov, Daniel M; Zhou, Rudy; Schmeltzer, Lauren; Dymov, Sergey; Szyf, Moshe.
I: Epigenomics, Bind 9, Nr. 5, 05.2017, s. 611-633.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - DNA methylation controls unmethylated transcription start sites in the genome in trans
AU - Cheishvili, David
AU - Christiansen, Steffan
AU - Stochinsky, Rebecca
AU - Pepin, Anne-Sophie
AU - Sapozhnikov, Daniel M
AU - Zhou, Rudy
AU - Schmeltzer, Lauren
AU - Dymov, Sergey
AU - Szyf, Moshe
PY - 2017/5
Y1 - 2017/5
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.2217/epi-2016-0141
DO - 10.2217/epi-2016-0141
M3 - Journal article
C2 - 28470094
VL - 9
SP - 611
EP - 633
JO - Epigenomics
JF - Epigenomics
SN - 1750-1911
IS - 5
ER -
ID: 182891694