Regulation of DNA methylation of Rasgrf1

Bongjune Yoon, Herry Herman, Aimee Sikora, Laura T. Smith, Christoph Plass, Paul D. Soloway

Research output: Contribution to journalArticle

132 Citations (Scopus)

Abstract

In mammals, DNA is methylated at cytosines within CpG dinucleotides. Properly regulated methylation is crucial for normal development. Inappropriate methylation may contribute to tumorigenesis by silencing tumor-suppressor genes or by activating growth-stimulating genes. Although many genes have been identified that acquire methylation and whose expression is methylation-sensitive, little is known about how DNA methylation is controlled. We have identified a DNA sequence that regulates establishment of DNA methylation in the male germ line at Rasgrf1. In mice, the imprinted Rasgrf1 locus is methylated on the paternal allele within a differentially methylated domain (DMD) 30 kbp 5′ of the promoter. Expression is exclusively from the paternal allele in neonatal brain. Methylation is regulated by a repeated sequence, consisting of a 41-mer repeated 40 times, found immediately 3′ of the DMD. This sequence is present in organisms in which Rasgrf1 is imprinted. In addition, DMD methylation is required for imprinted Rasgrf1 expression. Together the DMD and repeat element constitute a binary switch that regulates imprinting at the locus.

Original languageEnglish
Pages (from-to)92-96
Number of pages5
JournalNature Genetics
Volume30
Issue number1
DOIs
Publication statusPublished - 2002 Jan 1
Externally publishedYes

Fingerprint

ras-GRF1
DNA Methylation
Methylation
Alleles
Cytosine
Tumor Suppressor Genes
Germ Cells
Genes
Mammals
Carcinogenesis
DNA
Brain
Growth

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Yoon, B., Herman, H., Sikora, A., Smith, L. T., Plass, C., & Soloway, P. D. (2002). Regulation of DNA methylation of Rasgrf1. Nature Genetics, 30(1), 92-96. https://doi.org/10.1038/ng795

Regulation of DNA methylation of Rasgrf1. / Yoon, Bongjune; Herman, Herry; Sikora, Aimee; Smith, Laura T.; Plass, Christoph; Soloway, Paul D.

In: Nature Genetics, Vol. 30, No. 1, 01.01.2002, p. 92-96.

Research output: Contribution to journalArticle

Yoon, B, Herman, H, Sikora, A, Smith, LT, Plass, C & Soloway, PD 2002, 'Regulation of DNA methylation of Rasgrf1', Nature Genetics, vol. 30, no. 1, pp. 92-96. https://doi.org/10.1038/ng795
Yoon B, Herman H, Sikora A, Smith LT, Plass C, Soloway PD. Regulation of DNA methylation of Rasgrf1. Nature Genetics. 2002 Jan 1;30(1):92-96. https://doi.org/10.1038/ng795
Yoon, Bongjune ; Herman, Herry ; Sikora, Aimee ; Smith, Laura T. ; Plass, Christoph ; Soloway, Paul D. / Regulation of DNA methylation of Rasgrf1. In: Nature Genetics. 2002 ; Vol. 30, No. 1. pp. 92-96.
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