Transcription of mouse DNA methyltransferase 1 (Dnmt1) is regulated by both E2F-Rb-HDAC-dependent and -independent pathways

Hiromichi Kimura, Takahisa Nakamura, Tomoya Ogawa, Satoshi Tanaka, Kunio Shiota

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Abnormal expression of Dnmt1 in vivo induces cellular alterations such as transformation, and an increase in Dnmt1 mRNA plays a causal role in c-fos-, ras- and SV40 large T antigen-induced transformation of fibroblasts in vitro. Here, we have investigated the regulation of Dnmt1 transcription. We identified the promoter region and major transcription start sites of mouse Dnmt1 and found two important cis-elements within the core promoter region. One is an E2F binding site, and the other is a binding site for an as yet unidentified factor. Point mutations in the two cis-elements decreased promoter activity in both non-transformed and transformed cells. Thus, both sites play a critical role in regulation of Dnmt1 transcription in proliferating cells. Treatment with trichostatin A, a specific inhibitor of histone deacetylase, increased Dnmt1 promoter activity in G0/G1-arrested NIH 3T3 cells. Furthermore, the decrease in promoter activity induced by expression of E2F-1 and Rb was reversed by trichostatin A treatment of Saos-2 cells. Taken together, these data indicate that transcription of Dnmt1 is regulated in a complex fashion by E2F and other transcription factors through E2F-Rb-HDAC-dependent and -independent pathways. These findings suggest that Dnmt1 is a target gene of these pathways in cell proliferation, cell transformation and tumorigenesis.

Original languageEnglish
Pages (from-to)3101-3113
Number of pages13
JournalNucleic Acids Research
Volume31
Issue number12
DOIs
Publication statusPublished - 2003 Jun 15
Externally publishedYes

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Methyltransferases
DNA
trichostatin A
E2F Transcription Factors
Genetic Promoter Regions
Binding Sites
Polyomavirus Transforming Antigens
NIH 3T3 Cells
Histone Deacetylase Inhibitors
Transcription Initiation Site
Viral Tumor Antigens
Point Mutation
Carcinogenesis
Fibroblasts
Cell Proliferation
Messenger RNA
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Transcription of mouse DNA methyltransferase 1 (Dnmt1) is regulated by both E2F-Rb-HDAC-dependent and -independent pathways. / Kimura, Hiromichi; Nakamura, Takahisa; Ogawa, Tomoya; Tanaka, Satoshi; Shiota, Kunio.

In: Nucleic Acids Research, Vol. 31, No. 12, 15.06.2003, p. 3101-3113.

Research output: Contribution to journalArticle

Kimura, Hiromichi ; Nakamura, Takahisa ; Ogawa, Tomoya ; Tanaka, Satoshi ; Shiota, Kunio. / Transcription of mouse DNA methyltransferase 1 (Dnmt1) is regulated by both E2F-Rb-HDAC-dependent and -independent pathways. In: Nucleic Acids Research. 2003 ; Vol. 31, No. 12. pp. 3101-3113.
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