title: A novel homeodomain-encoding gene is associated with a large CpG island interrupted by the myotonic dystrophy unstable (CTG)n repeat.
abstract: Myotonic dystrophy (DM) is associated with a (CTG)n trinucleotide repeat expansion in the 3'-untranslated region of a protein kinase-encoding gene, DMPK, which maps to chromosome 19q13.3. Characterisation of the expression of this gene in patient tissues has thus far generated conflicting data on alterations in the steady state levels of DMPK mRNA, and on the final DMPK protein levels in the presence of the expansion. The DM region of chromosome 19 is gene rich, and it is possible that the repeat expansion may lead to dysfunction of a number of transcription units in the vicinity, perhaps as a consequence of chromatin disruption. We have searched for genes associated with a CpG island at the 3' end of DMPK. Sequencing of this region shows that the island extends over 3.5 kb and is interrupted by the (CTG)n repeat. Comparison of genomic sequences downstream (centromeric) of the repeat in human and mouse identified regions of significant homology. These correspond to exons of a gene predicted to encode a homeodomain protein. RT-PCR analysis shows that this gene, which we have called DM locus-associated homeodomain protein (DMAHP), is expressed in a number of human tissues, including skeletal muscle, heart and brain.
authors.affiliation: Department of Anatomy, Charing Cross and Westminster Medical School, London, UK.
authors.forename: C A
authors.initials: CA
authors.lastname: Boucher
authors.forename: S K
authors.initials: SK
authors.lastname: King
authors.forename: N
authors.initials: N
authors.lastname: Carey
authors.forename: R
authors.initials: R
authors.lastname: Krahe
authors.forename: C L
authors.initials: CL
authors.lastname: Winchester
authors.forename: S
authors.initials: S
authors.lastname: Rahman
authors.forename: T
authors.initials: T
authors.lastname: Creavin
authors.forename: P
authors.initials: P
authors.lastname: Meghji
authors.forename: M E
authors.initials: ME
authors.lastname: Bailey
authors.forename: F L
authors.initials: FL
authors.lastname: Chartier
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D002503:Centromere; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D003001:Cloning, Molecular; D015226:Dinucleoside Phosphates; D005091:Exons; D015870:Gene Expression; D015723:Gene Library; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009223:Myotonic Dystrophy / Q000201:enzymology / Q000235:genetics*; D065636:Myotonin-Protein Kinase; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic
chemical_list: D015226:Dinucleoside Phosphates; D018398:Homeodomain Proteins; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases; C585517:DMPK protein, human; C585516:DMPK protein, mouse; C106687:SIX5 protein, human; C486344:Six5 protein, mouse; C015772:CpG dinucleotide