Regulation of Human RNA Polymerase III Transcription by DNMT1 and DNMT3a DNA Methyltransferases

Selvakumar, Tharakeswari; Gjidoda, Alison; Hovde, Stacy; Henry, R. William

doi:10.1074/jbc.m111.285601

Cited by 25 publications

(31 citation statements)

References 62 publications

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“…In agreement with our results, U6 snRNA family genes, which are transcribed by RNA polymerase III, have been reported to be regulated by DNA methylation recently [26]. Increased expression of RNA polymerase III products is often observed in transformed cells [27].…”

Section: Resultssupporting

confidence: 92%

Genome-Wide Analysis of DNA Methylation and Expression of MicroRNAs in Breast Cancer Cells

Morita

Takahashi²,

Yamashita

et al. 2012

IJMS

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DNA methylation of promoters is linked to transcriptional silencing of protein-coding genes, and its alteration plays important roles in cancer formation. For example, hypermethylation of tumor suppressor genes has been seen in some cancers. Alteration of methylation in the promoters of microRNAs (miRNAs) has also been linked to transcriptional changes in cancers; however, no systematic studies of methylation and transcription of miRNAs have been reported. In the present study, to clarify the relation between DNA methylation and transcription of miRNAs, next-generation sequencing and microarrays were used to analyze the methylation and expression of miRNAs, protein-coding genes, other non-coding RNAs (ncRNAs), and pseudogenes in the human breast cancer cell lines MCF7 and the adriamycin (ADR) resistant cell line MCF7/ADR. DNA methylation in the proximal promoter of miRNAs is tightly linked to transcriptional silencing, as it is with protein-coding genes. In protein-coding genes, highly expressed genes have CpG-rich proximal promoters whereas weakly expressed genes do not. This is only rarely observed in other gene categories, including miRNAs. The present study highlights the epigenetic similarities and differences between miRNA and protein-coding genes.

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Section: Resultssupporting

confidence: 92%

Genome-Wide Analysis of DNA Methylation and Expression of MicroRNAs in Breast Cancer Cells

Morita

Takahashi²,

Yamashita

et al. 2012

IJMS

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show abstract

“…In this scenario, RB positioned distally to the nucleosome would similarly be brought into position to its targets within the core machinery by DNA wrapping. Consistent with the involvement of chromatinmodifying factors in RB regulation of Pol II transcription, RB expression by transient transfection facilitated DNMT1 recruitment to the RNU6-1 locus [116], suggesting that this and other chromatin modifying factors contribute to Pol III regulation during tumor suppression, a topic for future efforts. Together, these studies have uncovered an unanticipated diversity of RB tumor suppressor function in the control of Pol III.…”

Section: Genome-wide Analyses Of Rb and Rna Polymerase IIImentioning

confidence: 76%

RNA polymerase III repression by the retinoblastoma tumor suppressor protein

Gjidoda

Henry

2013

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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The Retinoblastoma (RB) tumor suppressor protein regulates multiple pathways that influence cell growth, and as a key regulatory node, its function is inactivated in most cancer cells. In addition to its canonical roles in cell cycle control, RB functions as a global repressor of RNA polymerase (Pol) III transcription. Indeed, Pol III transcripts accumulate in cancer cells and their heightened levels are implicated in accelerated growth associated with RB dysfunction. Herein we review the mechanisms of RB repression for the different types of Pol III genes. For type 1 and type 2 genes, RB represses transcription through direct contacts with the core transcription machinery, notably Brf1-TFIIIB, and inhibits preinitiation complex formation and Pol III recruitment. A contrasting model for type 3 gene repression indicates that RB regulation involves stable and simultaneous promoter association by RB, the general transcription machinery including SNAPc, and Pol III, suggesting that RB may impede Pol III promoter escape or elongation. Interestingly, analysis of published genomic association data for RB and Pol III revealed added regulatory complexity for Pol III genes both during active growth and during arrested growth associated with quiescence and senescence.

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“…Thus, we sought to determine if there were additional mechanisms regulating U6 expression, in addition to decreased p53 expression levels (Figure 3B). Previous experiments in breast cancer cell lines have demonstrated that U6 promoter methylation can be regulated by DNMTs [30], suggesting that U6 transcription may be regulated by epigenetic changes. Previously, the methylation status of the U6 promoter has not been determined in normal liver tissue from male C57BL/6J mice.…”

Section: Resultsmentioning

confidence: 99%