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Molecular and Cellular Biology, August 2000, p. 5808-5817, Vol. 20, No. 16
Metabolic Diseases Branch, National Institute
of Diabetes, Digestive and Kidney Diseases, National Institutes of
Health, Bethesda, Maryland 20892
Received 10 March 2000/Returned for modification 2 May
2000/Accepted 22 May 2000
The imprinted mouse gene Gnas produces the G protein
0270-7306/00/$04.00+0
Identification of a Methylation Imprint Mark
within the Mouse Gnas Locus
-subunit GS
and several other gene products by using
alternative promoters and first exons. GS
is maternally
expressed in some tissues and biallelically expressed in most
other tissues, while the gene products NESP55 and XL
s are maternally
and paternally expressed, respectively. We investigated the
mechanisms of Gnas imprinting. The GS
promoter and first exon are not methylated on either
allele. A further upstream region (approximately from positions
3400 to
939 relative to the GS
translational start
site) is methylated only on the maternal allele in all adult somatic
tissues and in early postimplantation development.
Within this region lies a fourth promoter and first exon (exon 1A)
that generates paternal-specific mRNAs of unknown function.
Exon 1A and GS
mRNAs have similar expression
patterns, making competition between their promoters unlikely.
Differential methylation in this region is established during
gametogenesis, being present in oocytes and absent in spermatozoa, and
is maintained in preimplantation E3.5d blastocysts. Therefore, this
region is a methylation imprint mark. In contrast, differential methylation of the NESP55 and XL
s promoter regions (Nesp
and Gnasxl) is not established during
gametogenesis. The methylation imprint mark that we identified may
be important for the tissue-specific imprinting of
GS
.
*
Corresponding author. Mailing address: Metabolic
Diseases Branch, NIDDK/NIH, Bldg. 10, Rm. 8C101, Bethesda, MD
20892-1752. Phone: (301) 402-2923. Fax: (301) 402-0374. E-mail:
leew{at}amb.niddk.nih.gov.
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