title: DLX5 and DLX6 expression is biallelic and not modulated by MeCP2 deficiency.
abstract: Mutations in MECP2 and Mecp2 (encoding methyl-CpG binding protein 2 [MeCP2]) cause distinct neurological phenotypes in humans and mice, respectively, but the molecular pathology is unclear. Recent literature claimed that the developmental homeobox gene DLX5 is imprinted and that its imprinting status is modulated by MeCP2, leading to biallelic expression in Rett syndrome and twofold overexpression of Dlx5 and Dlx6 in Mecp2-null mice. The conclusion that DLX5 is a direct target of MeCP2 has implications for research on the molecular bases of Rett syndrome, autism, and genomic imprinting. Attempting to replicate the reported data, we evaluated allele-specific expression of DLX5 and DLX6 in mouse x human somatic cell hybrids, lymphoblastoid cell lines, and frontal cortex from controls and individuals with MECP2 mutations. We identified novel single-nucleotide polymorphisms in DLX5 and DLX6, enabling the first imprinting studies of DLX6. We found that DLX5 and DLX6 are biallelically expressed in somatic cell hybrids and in human cell lines and brain, with no differences between affected and control samples. We also determined expression levels of Dlx5 and Dlx6 in forebrain from seven male Mecp2-mutant mice and eight wild-type littermates by real-time quantitative reverse-transcriptase polymerase chain reaction assays. Expression of Dlx5 and Dlx6, as well as of the imprinted gene Peg3, in mouse forebrain was highly variable, with no consistent differences between Mecp2-null mutants and controls. We conclude that DLX5 and DLX6 are not imprinted in humans and are not likely to be direct targets of MeCP2 modulation. In contrast, the imprinting status of PEG3 and PEG10 is maintained in MeCP2-deficient tissues. Our results confirm that MeCP2 plays no role in the maintenance of genomic imprinting and add PEG3 and PEG10 to the list of studied imprinted genes.
authors: Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors: Birgitt
authors: B
authors: Schüle
authors: Hong Hua
authors: HH
authors: Li
authors: Claudia
authors: C
authors: Fisch-Kohl
authors: Carolin
authors: C
authors: Purmann
authors: Uta
authors: U
authors: Francke
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D022981:Allelic Imbalance; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D002460:Cell Line; D002540:Cerebral Cortex / Q000737:chemistry / Q000378:metabolism; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D015870:Gene Expression; D018392:Genomic Imprinting; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D008875:Middle Aged; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics; D016601:RNA-Binding Proteins; D015518:Rett Syndrome / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D051017:Apoptosis Regulatory Proteins; C100596:DLX5 protein, human; C491014:DLX6 protein, human; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; D051783:Methyl-CpG-Binding Protein 2; C432965:PEG10 protein, human; C490820:PEG3 protein, human; D011506:Proteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors
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