Regulation of mammalian DNA methyltransferases: a route to new mechanisms

Denis, Hélène; Ndlovu, Matladi N.; Fuks, François

doi:10.1038/embor.2011.110

Cited by 327 publications

(263 citation statements)

References 88 publications

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“…DNMT1 is a maintenance methyltransferase, and DNMT3A and DNMT3B are de novo methyltransferases. Increasing evidence suggests a complex regulatory network of recruited DNMTs at specific genomic regions to establish common or individual DNA methylation patterns that depend on the cellular internal environment and regulation of extracellular signals (21,22). The results of this study indicate that FOXF2 transcription is communally and/or individually modulated by DNMT1, DNMT3A, and DNMT3B, which are specifically recruited to the FOXF2 promoter region in different non-basal-like breast cancer cells.…”

Section: Discussionmentioning

confidence: 57%

DNA Methylation Affects the SP1-regulated Transcription of FOXF2 in Breast Cancer Cells

Tian

Lun

Huang

et al. 2015

Journal of Biological Chemistry

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Background: Promoter hypermethylation affects the regulation of transcription factors for target genes. Results: SP1 activates FOXF2 transcription, but this activation is prevented through FOXF2 promoter methylation. Conclusion: FOXF2 transcription is regulated through the combined effects of DNA methylation and SP1 transcriptional regulation. Significance: Herein, we describe a new regulatory mechanism for the subtype-specific expression of FOXF2 in breast cancer.

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Section: Discussionmentioning

confidence: 57%

DNA Methylation Affects the SP1-regulated Transcription of FOXF2 in Breast Cancer Cells

Tian

Lun

Huang

et al. 2015

Journal of Biological Chemistry

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“…There are three enzymatically active mammalian DNMTs, namely DNMT 1 (DNMT1), DNMT 3 alpha (DNMT3A) and DNMT 3 beta (DNMT3B), and one related regulatory protein, DNMT 3-like (DNMT3L). The latter lacks catalytic activity (Denis et al, 2011). The most abundant of these is DNMT1, which is primarily responsible for maintenance and regulation of DNA methylation patterns, while DNMT3A and DNMT3B establish de novo methylation patterns which are then maintained by DNMT1 (Jones and Baylin, 2002;Okano et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-148a Can Regulate Runt-Related Transcription Factor 3 Gene Expression via Modulation of DNA Methyltransferase 1 in Gastric Cancer

Zuo

Xia

et al. 2013

Molecules and Cells

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Underexpression of the gene runt-related transcription factor 3 (RUNX3), an important tumor suppressor, is known to contribute to gastric cancer progression. However, the mechanism underlying aberrant RUNX3 expression has not been fully elucidated. We investigated the role of microRNA-148a (miR-148a) and DNA methyltransferases (DNMTs) in RUNX3 promoter methylation and gene expression. RUNX3 mRNA, RUNX3 protein, and methylation levels were assayed in human gastric cancer tissues and matched normal tissues, and AGS and BGC-823 cells by real-time reverse transcription PCR, Western blot, and methylation-specific PCR, respectively. A correlation between RUNX3 mRNA levels and that of miR-148a was also investigated in gastric cancer tissues. We found that RUNX3 mRNA levels were significantly downregulated in gastric cancer tissues compared with their matched normal tissues, and were closely associated with miR-148a expression. After treatment of human gastric cancer AGS and BGC-823 cells with the DNA methylation inhibitor 5-aza-2'-deoxycytidine, a significant increase in RUNX3 mRNA, RUNX3 protein, and the non-methylated form of the RUNX3 promoter were observed relative to untreated cells. Enforced expression of miR-148a, which can modulate DNMT1 and DNMT3B, also increased the expression of RUNX3 in gastric cancer cells. Knockdown of DNMT1 was associated with increased levels of RUNX3 mRNA and RUNX3 protein, while knockdown of DNMT3B did not have any effect on these in BGC-823 cells. Our results show that miR-148a may regulate RUNX3 expression through modulation of DNMT1-dependent DNA methylation in gastric cancer and highlight a miRNA-epigenetics regulation mechanism of gene expression.

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“…This effect was associated with reduced activity of the enzyme, DNA methylation methyl transferase 1 (DNMT1) in colorectal tumors (14). DNMT1 is chiefly responsible for DNA methylation homeostasis, whereas two other methyl transferases; i.e., DNMT3a and DNMT3b, primarily catalyze de novo hypermethylation (18). All three enzymes, DNMT1, DNMT3a, and DMNT3b, have been shown to be overexpressed in several tumor types, including colorectal cancer (14,19).…”

Section: Introductionmentioning

confidence: 99%

A Phase Ib Study of the Effects of Black Raspberries on Rectal Polyps in Patients with Familial Adenomatous Polyposis

Wang¹,

Burke

Hasson

et al. 2014

Cancer Prevention Research

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Familial adenomatous polyposis (FAP) is characterized by the early onset of colonic polyposis and a high risk for colorectal cancer. FAP is treated by colectomy followed by lifelong removal of rectal polyps. This study determined whether black raspberries (BRBs) might regress rectal polyps in patients with FAP. Fourteen patients with FAP were treated with BRBs daily for 9 months. Seven patients received BRB powder orally plus two BRB suppositories inserted into the rectum at bedtime. The other 7 received an oral placebo plus the suppositories. Rectal polyp counts and polyp sizes were obtained at time zero and after 9 months of BRB treatment. Polyps and adjacent normal tissue were collected at both time points. The burden (P ¼ 0.036) but not number (P ¼ 0.069) of rectal polyps was significantly decreased. No benefit was noted with the addition of oral BRBs. Three patients were nonresponders. BRBs significantly decreased cellular proliferation, DNA methylation methyl transferase 1 protein expression, and p16 promoter methylation, but not promoter methylation of the Wnt pathway antagonists, SFRP2 and WIF1, in rectal polyps (adenomas) from responders but not from nonresponders. The MBD-seq assay revealed more demethylated transcription start sites (TSS), including those for miRNAs, in BRB-treated adenomas from the responders. In conclusion, BRB suppositories seem sufficient for regressing rectal polyps in patients with FAP. Cancer Prev Res; 7(7); 666-74. Ó2014 AACR.

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Regulation of mammalian DNA methyltransferases: a route to new mechanisms

Cited by 327 publications

References 88 publications

DNA Methylation Affects the SP1-regulated Transcription of FOXF2 in Breast Cancer Cells

DNA Methylation Affects the SP1-regulated Transcription of FOXF2 in Breast Cancer Cells

MicroRNA-148a Can Regulate Runt-Related Transcription Factor 3 Gene Expression via Modulation of DNA Methyltransferase 1 in Gastric Cancer

A Phase Ib Study of the Effects of Black Raspberries on Rectal Polyps in Patients with Familial Adenomatous Polyposis

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