title: The human HYMAI/PLAGL1 differentially methylated region acts as an imprint control region in mice.
abstract: Imprinting centers (IC) can be defined as cis-elements that are recognized in the germ line and are epigenetically modified to bring about the full imprinting program in a somatic cell. Two paternally expressed human genes, HYMAI and PLAGL1 (LOT1/ZAC), are located within human chromosome 6q24. Within this region lies a 1-kb CpG island that is differentially methylated in somatic cells, unmethylated in sperm, and methylated in mature oocytes in mice, characteristic features of an IC. Loss of methylation of the homologous region in humans is observed in patients with transient neonatal diabetes mellitus and hypermethylation is associated with a variety of cancers, suggesting that this region regulates the expression of one or more key genes in this region involved in these diseases. We now report that a transgene carrying the human HYMAI/PLAGL1 DMR was methylated in the correct parent-origin-specific manner in mice and this was sufficient to confer imprinted expression from the transgene. Therefore, we propose that this DMR functions as the IC for the HYMAI/PLAGL1 domain.
authors.affiliation: Division of Molecular and Cell Therapeutics, Department of Molecular Genetics, Kyusyu University, Beppu, Oita 874-0838, Japan. tarima@tsurumi.beppu.kyushu-u.ac.jp
authors.forename: Takahiro
authors.initials: T
authors.lastname: Arima
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Yamasaki
authors.forename: Rosalind M
authors.initials: RM
authors.lastname: John
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Kato
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Sakumi
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Nakabeppu
authors.forename: Norio
authors.initials: N
authors.lastname: Wake
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kono
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D017931:DNA Primers / Q000235:genetics; D005260:Female; D015870:Gene Expression; D020868:Gene Silencing; D017930:Genes, Reporter; D018392:Genomic Imprinting; D023281:Genomics; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009865:Oocytes / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics*; D013094:Spermatozoa / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D017931:DNA Primers; C509782:HYMAI, RNA; C106464:PLAGL1 protein, human; D012333:RNA, Messenger; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins