title: Expansion of stochastic expression repertoire by tandem duplication in mouse Protocadherin-α cluster.
abstract: Tandem duplications are concentrated within the Pcdh cluster throughout vertebrate evolution and as copy number variations (CNVs) in human populations, but the effects of tandem duplication in the Pcdh cluster remain elusive. To investigate the effects of tandem duplication in the Pcdh cluster, here we generated and analyzed a new line of the Pcdh cluster mutant mice. In the mutant allele, a 218-kb region containing the Pcdh-α2 to Pcdh-αc2 variable exons with their promoters was duplicated and the individual duplicated Pcdh isoforms can be disctinguished. The individual duplicated Pcdh-α isoforms showed diverse expression level with stochastic expression manner, even though those have an identical promoter sequence. Interestingly, the 5'-located duplicated Pcdh-αc2, which is constitutively expressed in the wild-type brain, shifted to stochastic expression accompanied by increased DNA methylation. These results demonstrate that tandem duplication in the Pcdh cluster expands the stochastic expression repertoire irrespective of sequence divergence.
authors.affiliation: Bioresource center, Gunma University Graduate School of Medicine.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kaneko
authors.affiliation: Department of Cellular Neurobiology, Brain Research Institute, Niigata University.
authors.forename: Manabu
authors.initials: M
authors.lastname: Abe
authors.affiliation: KOKORO-Biology Group, Laboratories for Integrated Biology, Graduate School of Frontier Biosciences, Osaka University.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hirabayashi
authors.affiliation: KOKORO-Biology Group, Laboratories for Integrated Biology, Graduate School of Frontier Biosciences, Osaka University.
authors.forename: Arikuni
authors.initials: A
authors.lastname: Uchimura
authors.affiliation: Department of Cellular Neurobiology, Brain Research Institute, Niigata University.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakimura
authors.affiliation: 1] Bioresource center, Gunma University Graduate School of Medicine [2] Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine [3] Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (CREST).
authors.forename: Yuchio
authors.initials: Y
authors.lastname: Yanagawa
authors.affiliation: 1] KOKORO-Biology Group, Laboratories for Integrated Biology, Graduate School of Frontier Biosciences, Osaka University [2] Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (CREST).
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yagi
mesh_terms: D000483:Alleles; D000818:Animals; D001921:Brain / Q000378:metabolism; D015820:Cadherins / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics; D020080:Tandem Repeat Sequences / Q000235:genetics*
chemical_list: D015820:Cadherins; D020033:Protein Isoforms