Discovery of a novel, paternally expressed ubiquitin-specific processing protease gene through comparative analysis of an imprinted region of mouse chromosome 7 and human chromosome 19q13.4.

Using mouse BAC clones spanning an imprinted interval of proximal mouse chromosome 7 and the genomic sequence of the related interval of human chromosome 19q13.4, we have identified a novel mouse gene, Usp29 (ubiquitin-specific processing protease 29), near two known imprinted genes, Peg3 and Zim1. Gene Usp29 is located directly adjacent to Peg3 in a "head-to-head" orientation, and comprises exons distributed over a genomic distance of at least 400 kb. A similar human gene is also found in the homologous location in human chromosome 19q13.4. The mouse Usp29 gene is also imprinted and is transcribed mainly from the paternal allele with highest expression levels in adult brain, especially in the cerebral cortex and hippocampus, and in the forebrain, face, and limb buds of midgestation mouse embryos. Analysis of a full-length 7.6-kb cDNA clone revealed that Usp29 encodes an 869-amino-acid protein that displays significant homology with yeast and nematode ubiquitin carboxyl-terminal hydrolases. These data suggest that, like the candidate Angelman syndrome gene Ube3a (ubiquitin ligase), Usp29 may represent another imprinted gene involved in the ubiquitination pathway. This identification of a third imprinted gene, Usp29, from the Peg3/Zim1-region confirms the presence of a conserved imprinted domain spanning at least 500 kb in the proximal portion of mouse chromosome 7 (Mmu7).

[1]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[2]  L. Stubbs,et al.  Exon sharing of a novel human zinc-finger gene, ZIM2, and paternally expressed gene 3 (PEG3). , 2000, Genomics.

[3]  M. Surani,et al.  Organization and parent-of-origin-specific methylation of imprinted Peg3 gene on mouse proximal chromosome 7. , 2000, Genomics.

[4]  J. Beckmann,et al.  Human-mouse differences in the embryonic expression patterns of developmental control genes and disease genes. , 2000, Human molecular genetics.

[5]  L. Stubbs,et al.  Zim1, a maternally expressed mouse Kruppel-type zinc-finger gene located in proximal chromosome 7. , 1999, Human molecular genetics.

[6]  V. Stanton,et al.  Screening Large‐Insert Libraries by Hybridization , 1999 .

[7]  D. J. Driscoll,et al.  A novel imprinted gene, encoding a RING zinc-finger protein, and overlapping antisense transcript in the Prader-Willi syndrome critical region. , 1999, Human molecular genetics.

[8]  E. Keverne,et al.  Regulation of maternal behavior and offspring growth by paternally expressed Peg3. , 1999, Science.

[9]  S. Tilghman.  The Sins of the Fathers and Mothers Genomic Imprinting in Mammalian Development , 1999, Cell.

[10]  M. Azim Surani,et al.  Abnormal maternal behaviour and growth retardation associated with loss of the imprinted gene Mest , 1998, Nature Genetics.

[11]  A. Reeve,et al.  A catalogue of imprinted genes and parent-of-origin effects in humans and animals. , 1998, Human molecular genetics.

[12]  S. Saitoh,et al.  Imprinting in Prader-Willi and Angelman syndromes. , 1998, Trends in genetics : TIG.

[13]  Carlos Cardoso,et al.  An imprinted antisense RNA overlaps UBE3A and a second maternally expressed transcript , 1998, Nature Genetics.

[14]  R. Raff,et al.  Evolutionary changes in sites and timing of actin gene expression in embryos of the direct- and indirect-developing sea urchins, Heliocidaris erythrogramma and H. tuberculata , 1998, Development Genes and Evolution.

[15]  S. Tilghman,et al.  Competitive edge at the imprinted Prader-Willi/Angelman region? , 1998, Nature Genetics.

[16]  D. Barlow.  Competition—a common motif for the imprinting mechanism? , 1997, The EMBO journal.

[17]  K. Wilkinson.  Regulation of ubiquitin‐dependent processes by deubiquitinating enzymes , 1997, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[18]  L. Stubbs,et al.  Amplification and sequencing of end fragments from bacterial artificial chromosome clones by single-primer polymerase chain reaction. , 1997, Analytical Biochemistry.

[19]  T. Moore,et al.  Multiple imprinted sense and antisense transcripts, differential methylation and tandem repeats in a putative imprinting control region upstream of mouse Igf2. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[20]  E. Wagner,et al.  Imprinted expression of the Igf2r gene depends on an intronic CpG island , 1997, Nature.

[21]  W. Reik,et al.  Imprinting in clusters: lessons from Beckwith-Wiedemann syndrome. , 1997, Trends in genetics : TIG.

[22]  L. Ashworth,et al.  The human homolog of a mouse-imprinted gene, Peg3, maps to a zinc finger gene-rich region of human chromosome 19q13.4. , 1997, Genome research.

[23]  A. Feinberg,et al.  Human KVLQT1 gene shows tissue-specific imprinting and encompasses Beckwith-Wiedemann syndrome chromosomal rearrangements , 1997, Nature Genetics.

[24]  M. Lalande,et al.  UBE3A/E6-AP mutations cause Angelman syndrome , 1996, Nature Genetics.

[25]  A. Smit,et al.  The origin of interspersed repeats in the human genome. , 1996, Current opinion in genetics & development.

[26]  A. Poustka,et al.  Imprint switching on human chromosome 15 may involve alternative transcripts of the SNRPN gene , 1996, Nature Genetics.

[27]  J. Marsh,et al.  Evolutionary changes in the expression pattern of a developmentally essential gene in three Drosophila species. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[28]  M. Surani,et al.  Peg3 imprinted gene on proximal chromosome 7 encodes for a zinc finger protein , 1996, Nature Genetics.

[29]  X. Chen,et al.  Specific cloning of human DNA as yeast artificial chromosomes by transformation-associated recombination. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[30]  D. Barlow,et al.  Gametic Imprinting in Mammals , 1995, Science.

[31]  R. Nicholls,et al.  New insights reveal complex mechanisms involved in genomic imprinting. , 1994, American journal of human genetics.

[32]  C. Beechey,et al.  Genome imprinting phenomena on mouse chromosome 7. , 1990, Genetical research.

[33]  H. Lehrach,et al.  The HOX-5 and surfeit gene clusters are linked in the proximal portion of mouse chromosome 2. , 1990, Genomics.

[34]  M. Frohman,et al.  Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[35]  M. Bartolomei,et al.  Genomic imprinting in mammals. , 1997, Annual review of genetics.

[36]  T. Moore,et al.  Imprinted genes have few and small introns , 1996, Nature Genetics.

[37]  B. Cattanach,et al.  Genetic imprinting map. , 1990 .

[38]  M. Ashburner.  A Laboratory manual , 1989 .

[39]  C. A. Thomas,et al.  Molecular cloning. , 1977, Advances in pathobiology.