title: Narrowed abrogation of the Angelman syndrome critical interval on human chromosome 15 does not interfere with epigenotype maintenance in somatic cells.
abstract: Human chromosome 15q11-q13 involves a striking imprinted gene cluster of more than 2 Mb that is concomitant with multiple neurological disorders manifested by Prader-Willi syndrome (PWS) and Angelman syndrome (AS). PWS and AS patients with imprinting mutation have microdeletions, which share a 4.3 kb short region of overlap (SRO) at the 5' end of the paternal SNURF-SNRPN gene in PWS, or on the maternal allele, which shares a 880 bp SRO located at the 35 kb upstream of the SNURF-SNRPN promoter in AS. Recent studies have revealed an essential role of PWS-SRO in the postzygotic maintenance of the appropriate epigenotype on the paternal chromosome. For AS-SRO, however, there is insufficient experimental evidence exists to determine the direct functions. Here we show that the complete deletion of AS-SRO does not cause any anomalies of imprinted gene expression or DNA methylation on the mutated human chromosome 15, further supporting the idea that AS-SRO is dispensable for post implantation imprint maintenance. This implies that AS-SRO is not essential for the robust epigenotype preservation in somatic cells.
authors.affiliation: Division of Molecular and Cell Genetics, Department of Molecular and Cellular Biology, School of Life Sciences, Faculty of Medicine, Tottori University, Tottori, Japan.|Division of Cancer Diagnosis, Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Haruta
authors.affiliation: Division of Molecular and Cell Genetics, Department of Molecular and Cellular Biology, School of Life Sciences, Faculty of Medicine, Tottori University, Tottori, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Meguro
authors.affiliation: Division of Molecular and Cell Genetics, Department of Molecular and Cellular Biology, School of Life Sciences, Faculty of Medicine, Tottori University, Tottori, Japan.
authors.forename: Yu-Ki
authors.initials: YK
authors.lastname: Sakamoto
authors.affiliation: Department of Biomedical Science, Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Tottori, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Hoshiya
authors.affiliation: Division of Laboratory Animal Science, Research Center for Bioscience and Technology, Tottori University, Tottori, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Kashiwagi
authors.affiliation: Division of Cancer Diagnosis, Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kaneko
authors.affiliation: Biofunctional Science, Tohoku University Biomedical Engineering Research Organization (TUBERO), Sendai, Japan.
authors.forename: Kohzoh
authors.initials: K
authors.lastname: Mitsuya
authors.affiliation: Division of Molecular and Cell Genetics, Department of Molecular and Cellular Biology, School of Life Sciences, Faculty of Medicine, Tottori University, Tottori, Japan. oshimura@grape.med.tottori-u.ac.jp.|Department of Biomedical Science, Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Tottori, Japan. oshimura@grape.med.tottori-u.ac.jp.|Department of Human Genome Sciences (Kirin Brewery), Graduate School of Medical Science, Tottori University, Tottori, Japan. oshimura@grape.med.tottori-u.ac.jp.|Department of Biomedical Science, Regenerative Medicine and Biofunction, Graduate School of Medical Sciences, Tottori University, 86 Nishi-cho, Yonago, Tottori, 683-8503, Japan. oshimura@grape.med.tottori-u.ac.jp.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Oshimura
mesh_terms: D017204:Angelman Syndrome / Q000235:genetics*; D000818:Animals; D015139:Blotting, Southern; D002478:Cells, Cultured; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D020732:Cytogenetic Analysis; D019175:DNA Methylation; D017931:DNA Primers; D017353:Gene Deletion; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D018392:Genomic Imprinting / Q000235:genetics*; D006801:Humans; D051379:Mice; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D009687:Nuclear Proteins; C445239:SNURF protein, human
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