Human Molecular Genetics Advance Access originally published online on February 19, 2004
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Human Molecular Genetics, 2004, Vol. 13, No. 8 819-828
DOI: 10.1093/hmg/ddh098
Tissue-specific imprinting of the G protein Gs
is associated with tissue-specific differences in histone methylation
Metabolic Diseases Branch, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Received December 9, 2003; Accepted February 10, 2004
The G protein Gs
is imprinted in a tissue-specific manner, being primarily expressed from the maternal allele in some tissues, such as renal proximal tubules. The Gs promoter is unmethylated, but is downstream of a differentially methylated region [the exon 1A differentially methylated region (DMR)] that is methylated on the maternal allele. Maternal Gs null mutations or loss of maternal-specific exon 1A methylation leads to pseudohypoparathyroidism types 1A or 1B, respectively. We now have examined the chromatin state of each parental allele within the exon 1A-Gs promoter region by chromatin immunoprecipitation of samples derived from mice with heterozygous deletions within the region using antibodies to covalently modified histones. The exon 1A DMR had allele-specific differences in histone acetylation and methylation, with histone acetylation and H3 lysine 4 (H3K4) methylation of the paternal allele, and H3 lysine 9 (H3K9) methylation of the maternal allele. Both parental alleles had similar levels of histone acetylation and H3K4 methylation within the Gs promoter and first exon, with no H3K9 methylation. In liver, where Gs is biallelically expressed, both parental alleles had similar levels of tri- and dimethylated H3K4 within the Gs first exon. In contrast, in renal proximal tubules there was a greater ratio of tri- to dimethylated H3K4 of Gs exon 1 in the more transcriptionally active maternal as compared with the paternal allele. These results show that allele-specific differences in Gs expression correlate in a tissue-specific manner with allele-specific differences in the extent of H3K4 methylation, and are the first demonstration that chronic transcriptional activation in mammals is correlated with trimethylation of H3K4.
* To whom correspondence should be addressed. Tel: +1 3014022923; Fax: +1 3014020374; Email: leew{at}amb.niddk.nih.gov
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