Clcn4-2 genomic structure differs between the X locus in Mus spretus and the autosomal locus in Mus musculus: AT motif enrichment on the X

  1. Christine M. Disteche1,2,9
  1. 1Department of Pathology, University of Washington, Seattle, Washington 98195, USA;
  2. 2Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA;
  3. 3Department of Medicine, University of Washington, Seattle, Washington 98195, USA;
  4. 4Howard Hughes Medical Institute, Seattle, Washington 98195, USA;
  5. 5Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA;
  6. 6Department of Neurology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA;
  7. 7Children's Hospital, Oakland Research Institute, Oakland, California 94609, USA
    1. 8 These authors contributed equally to this work.

    Abstract

    In Mus spretus, the chloride channel 4 gene Clcn4-2 is X-linked and dosage compensated by X up-regulation and X inactivation, while in the closely related mouse species Mus musculus, Clcn4-2 has been translocated to chromosome 7. We sequenced Clcn4-2 in M. spretus and identified the breakpoints of the evolutionary translocation in the Mus lineage. Genetic and epigenetic differences were observed between the 5′ends of the autosomal and X-linked loci. Remarkably, Clcn4-2 introns have been truncated on chromosome 7 in M. musculus as compared with the X-linked loci from seven other eutherian mammals. Intron sequences specifically preserved in the X-linked loci were significantly enriched in AT-rich oligomers. Genome-wide analyses showed an overall enrichment in AT motifs unique to the eutherian X (except for genes that escape X inactivation), suggesting a role for these motifs in regulation of the X chromosome.

    Footnotes

    • Received March 30, 2010.
    • Accepted December 15, 2010.

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