RGD Reference Report - Role of histone methyltransferase G9a in CpG methylation of the Prader-Willi syndrome imprinting center. - Rat Genome Database

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Role of histone methyltransferase G9a in CpG methylation of the Prader-Willi syndrome imprinting center.

Authors: Xin, Z  Tachibana, M  Guggiari, M  Heard, E  Shinkai, Y  Wagstaff, J 
Citation: Xin Z, etal., J Biol Chem 2003 Apr 25;278(17):14996-5000. Epub 2003 Feb 13.
RGD ID: 1304480
Pubmed: PMID:12586828   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M211753200   (Journal Full-text)

Imprinted genes in mammals are often located in clusters whose imprinting is subject to long range regulation by cis-acting sequences known as imprinting centers (ICs). The mechanisms by which these ICs exert their effects is unknown. The Prader-Willi syndrome IC (PWS-IC) on human chromosome 15 and mouse chromosome 7 regulates imprinted gene expression bidirectionally within an approximately 2-megabase region and shows CpG methylation and histone H3 Lys-9 methylation in somatic cells specific for the maternal chromosome. Here we show that histone H3 Lys-9 methylation of the PWS-IC is reduced in mouse embryonic stem (ES) cells lacking the G9a histone H3 Lys-9/Lys-27 methyltransferase and that maintenance of CpG methylation of the PWS-IC in mouse ES cells requires the function of G9a. We show by RNA fluorescence in situ hybridization (FISH) that expression of Snrpn, an imprinted gene regulated by the PWS-IC, is biallelic in G9a -/- ES cells, indicating loss of imprinting. By contrast, Dnmt1 -/- ES cells lack CpG methylation of the PWS-IC but have normal levels of H3 Lys-9 methylation of the PWS-IC and show normal monoallelic Snrpn expression. Our results demonstrate a role for histone methylation in the maintenance of parent-specific CpG methylation of imprinting regulatory regions and suggest a possible role of histone methylation in establishment of these CpG methylation patterns.

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Gene Ehmt2 euchromatic histone lysine methyltransferase 2 Rattus norvegicus

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