Open AccessThe callipyge mutation enhances bidirectional long-range DLK1-GTL2 intergenic transcription in cis
Author(s) -
Hitoshi Takeda,
Florian Caiment,
Maria A. Smit,
Samuel Hiard,
Xavier Tordoir,
Noelle Cockett,
Michel Georges,
Carole Charlier
Publication year - 2006
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0602844103
Subject(s) - biology , genetics , transcription (linguistics) , ectopic expression , gene , philosophy , linguistics
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-kbDLK1-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 theCLPG mutation alters the muscular epigenotype of theDLK1-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.