title: The callipyge mutation enhances bidirectional long-range DLK1-GTL2 intergenic transcription in cis.
abstract: The callipyge mutation (CLPG) is an A to G transition that affects a muscle-specific long-range control element located in the middle of the 90-kb DLK1-GTL2 intergenic (IG) region. It causes ectopic expression of a 327-kb cluster of imprinted genes in skeletal muscle, resulting in the callipyge muscular hypertrophy and its non-Mendelian inheritance pattern known as polar overdominance. We herein demonstrate that the CLPG mutation alters the muscular epigenotype of the DLK1-GTL2 IG region in cis, including hypomethylation, acquisition of novel DNase-I hypersentivite sites, and, most strikingly, strongly enhanced bidirectional, long-range IG transcription. The callipyge phenotype thus emerges as a unique model to study the functional significance of IG transcription, which recently has proven to be a widespread, yet elusive, feature of the mammalian genome.
authors.affiliation: Unit of Animal Genetics, Faculty of Veterinary Medicine and Centre of Biomedical Integrative Genoproteomics (CBIG), University of Liège (B43), 20 Boulevard de Colonster, 4000-Liège, Belgium.
authors.forename: Haruko
authors.initials: H
authors.lastname: Takeda
authors.forename: Florian
authors.initials: F
authors.lastname: Caiment
authors.forename: Maria
authors.initials: M
authors.lastname: Smit
authors.forename: Samuel
authors.initials: S
authors.lastname: Hiard
authors.forename: Xavier
authors.initials: X
authors.lastname: Tordoir
authors.forename: Noelle
authors.initials: N
authors.lastname: Cockett
authors.forename: Michel
authors.initials: M
authors.lastname: Georges
authors.forename: Carole
authors.initials: C
authors.lastname: Charlier
mesh_terms: D000483:Alleles; D000818:Animals; D002135:Calcium-Binding Proteins; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental; D005799:Genes, Dominant; D005838:Genotype; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D011506:Proteins / Q000235:genetics*; D062085:RNA, Long Noncoding; D012097:Repressor Proteins / Q000235:genetics*; D012756:Sheep; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; C422882:MEG3 non-coding RNA, mouse; D008565:Membrane Proteins; D011506:Proteins; D062085:RNA, Long Noncoding; D012097:Repressor Proteins