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PMID: 11753386 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Regulation of DNA methylation of Rasgrf1.

Nature genetics ·Vol. 30 ·No. 1 ·2002-01-00 ·Pages 92-6

Yoon BJ, Herman H, Sikora A, Smith LT, Plass C, Soloway PD

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.

MeSH Terms
Alleles Animals CpG Islands Crosses, Genetic DNA Methylation Female Gene Expression Regulation Gene Targeting Genomic Imprinting Male Mice Mice, Inbred C57BL Polymorphism, Restriction Fragment Length Regulatory Sequences, Nucleic Acid Reverse Transcriptase Polymerase Chain Reaction Transgenes ras-GRF1/genetics
Chemicals
ras-GRF1
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Yoon Bong June
Dept. of Molecular and Cellular Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York 14263, USA.
Herman Herry
Sikora Aimee
Smith Laura T
Plass Christoph
Soloway Paul D
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1061-4036
DOI
10.1038/ng795
Published
2002-01-00
Epub
2001-00-20
Pages
92-6
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC2756564
Subset
IM
Grants
NCI NIH HHS · R01 CA098597 · United States
NCI NIH HHS · R01 CA098597-01 · United States
External Links
PubMed source DOI: 10.1038/ng795 PMC Full Text View journal details
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