Mammalian Genome

, Volume 15, Issue 3, pp 162–178 | Cite as

Sequence organization and matrix attachment regions of the human serine protease inhibitor gene cluster at 14q32.1

  • Stephanie J. Namciu
  • Richard D. Friedman
  • Mark D. Marsden
  • Lourdes M. Sarausad
  • Christine L. Jasoni
  • R. E. K. Fournier
Original Contribution

Abstract

The human serine protease inhibitor (serpin) gene cluster at 14q32.1 is a useful model system for studying the regulation of gene activity and chromatin structure. We demonstrated previously that the six known serpin genes in this region were organized into two subclusters of three genes each that occupied ~370 kb of DNA. To more fully understand the genomic organization of this region, we annotated a 1-Mb sequence contig from data from the Genoscope sequencing consortium (http://www.genoscope.cns.fr/ ). We report that 11 different serpin genes reside within the 14q32.1 cluster, including two novel α1-antiproteinase-like gene sequences, a kallistatin-like sequence, and two recently identified serpins that had not been mapped previously to 14q32.1. The genomic regions proximal and distal to the serpin cluster contain a variety of unrelated gene sequences of diverse function. To gain insight into the chromatin organization of the region, sequences with putative nuclear matrix-binding potential were identified by using the MAR-Wiz algorithm, and these MAR-Wiz candidate sequences were tested for nuclear matrix-binding activity in vitro. Several differences between the MAR-Wiz predictions and the results of biochemical tests were observed. The genomic organization of the serpin gene cluster is discussed.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Billingsley, GD, Walter, MA, Hammond, GL, Cox, DW 1993Physical mapping of four serpin genes: alpha 1-antitrypsin, alpha 1-antichymotrypsin, corticosteroid-binding globulin, and protein C inhibitor, within a 280-kb region on chromosome 14q32.1.Am J Hum Gene52343353PubMedGoogle Scholar
  2. 2.
    Blum, M, De Robertis, EM, Kojis, T, Heinzmann, C, Klisak, I,  et al. 1994Molecular cloning of the human homeobox gene goosecoid (GSC) and mapping of the gene to human chromosome 14q32.1.Genomics21388393CrossRefPubMedGoogle Scholar
  3. 3.
    Broeker, PL, Super, HB, Thirman, MJ, Pomykala, H, Yonebayashi, Y,  et al. 1996Distribution of 11q23 breakpoints within the MLL breakpoint cluster region in de novo acute leukemia and in treatment-related acute myeloid leukemia: correlation with scaffold attachment regions and topoisomerase II consenus binding sites.Blood8719121922PubMedGoogle Scholar
  4. 4.
    Burge, C, Karlin, S 1997Prediction of complete gene structures in human genomic DNA.J Mol Biol2687894CrossRefPubMedGoogle Scholar
  5. 5.
    Carrell, RW, Pemberton, PA, Boswell, DR 1987The serpins: evolution and adaptation in a family of protease inhibitors.Cold Spring Harbor Symp Quanti Biol52527535Google Scholar
  6. 6.
    Cockerill, PN, Garrard, WT 1986Chromosomal loop anchorage of the kappa immunoglobulin gene occurs next to the enhancer in a region containing topoisomerase II sites.Cell44273282PubMedGoogle Scholar
  7. 7.
    Dieken, ES, Epner, EM, Fiering, S, Fournier, REK, Groudine, M 1996Efficient modification of human chromosomal alleles using recombination-proficient chicken/human microcell hybrids.Nature Genet12174182PubMedGoogle Scholar
  8. 8.
    Frazer, JK, Jackson, DG, Gaillard, JP, Lutter, M, Liu, YJ,  et al. 2000Identification of centerin: a novel human germinal center B cell-restricted serpin.Europ J Immuno3030393048CrossRefGoogle Scholar
  9. 9.
    Gasser, SM, Laemmli, UK 1986Cohabitation of scaffold binding regions with upstream/enhancer elements of three developmentally regulated genes of D.melanogaster.Cell46521530PubMedGoogle Scholar
  10. 10.
    Gettins, PG 2000Keeping the serpin machine running smoothly.Genome Res1018331835CrossRefPubMedGoogle Scholar
  11. 11.
    Glazko, GV, Rogozin, IB, Glazkov, MV 2001Comparative study and prediction of DNA fragments associated with various elements of the nuclear matrix.Biochim Biophy Acta1517351364CrossRefGoogle Scholar
  12. 12.
    Hammond, GL, Smith, CL, Underhill, DA 1991Molecular studies of corticosteroid binding globulin structure, biosynthesis and function.J Steroid Biochem Mol Biol40755762CrossRefPubMedGoogle Scholar
  13. 13.
    Han, X, Huang, ZF, Fiehler, R, Broze Jr, GJ 1999The protein Z-dependent protease inhibitor is a serpin.Biochemistry381107311078CrossRefPubMedGoogle Scholar
  14. 14.
    Han, X, Fiehler, R, Broze, GJ 2000Characterization of the protein Z-dependent protease inhibitor.Blood9630493055PubMedGoogle Scholar
  15. 15.
    Heilig, R, Eckenberg, R, Petit, JL, Fonknechten, N, Da Silva, C,  et al. 2003The DNA sequence and analysis of human chromosome 14.Nature.421601607CrossRefPubMedGoogle Scholar
  16. 16.
    Irving, JA, Pike, RN, Lesk, AM, Whisstock, JC 2000Phylogeny of the serpin superfamily: implications of patterns of amino acid conservation for structure and function.Genome Res101845l864CrossRefPubMedGoogle Scholar
  17. 17.
    Izaurralde, E, Mirkovitch, J, Laemmli, UK 1988Interaction of DNA with nuclear scaffolds in vitro.J Mol Biol200111125PubMedGoogle Scholar
  18. 18.
    Jackers, P, Clausse, N, Fernandez, M, Berti, A, Princen, F,  et al. 1996Seventeen copies of the human 37 kDa laminin receptor precursor/p40 ribosome-associated protein gene are processed pseudogenes arisen from retropositional events.Biochim Biophys Acta130598104CrossRefPubMedGoogle Scholar
  19. 19.
    Kellum, R, Elgin, SC 1998Chromatin boundaries: punctuating the genome.Curr Biol8R521R524PubMedGoogle Scholar
  20. 20.
    Kent, WJ, Sugnet, CW, Furey, TS, Roskin, KM, Pringle, TH,  et al. 2002The human genome browser at UCSC.Genome Res12656664Google Scholar
  21. 21.
    Levy-Wilson, B, Fortier, C 1989The limits of the DNase I-sensitive domain of the human apolipoprotein B gene coincide with the locations of chromosomal anchorage loops and define the 5′ and 3′ boundaries of the gene.J Biol Chem2642119621204PubMedGoogle Scholar
  22. 22.
    Marsden, MD, Fournier, REK 2003Chromosomal elements regulate gene activity and chromatin structure of the human serpin gene cluster at 14q32.1.Mol Cell Biol2335163526CrossRefPubMedGoogle Scholar
  23. 23.
    Marshall, CJ 1993Evolutionary relationships among the serpins.Phil Trans R Soc London—Ser B: Biol Sci342101119Google Scholar
  24. 24.
    Mirkovitch, J, Mirault, ME, Laemmli, UK 1984Organization of the higher-order chromatin loop: specific DNA attachment sites on nuclear scaffold.Cell39223232PubMedGoogle Scholar
  25. 25.
    Murakami, K, Takagi, T 1998Gene recognition by combination of several gene-finding programs.Bioinformatics4665675CrossRefGoogle Scholar
  26. 26.
    Nagase, T, Kikuno, R, Ishikawa, K, Hirosawa, M, Ohara, O 2000Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.DNA Res7143150PubMedGoogle Scholar
  27. 27.
    Paulson, JR, Laemmli, UK 1977The structure of histone-depleted metaphase chromosomes.Cell12817828PubMedGoogle Scholar
  28. 28.
    Phi-Van, L, Stratling, WH 1996Dissection of the ability of the chicken lysozyme gene 5′ matrix attachment region to stimulate transgene expression and to dampen position effects.Biochemistry351073510742CrossRefPubMedGoogle Scholar
  29. 29.
    Rasmussen, UB, Wolf, C, Mattei, MG, Chenard, MP, Bellocq, JP,  et al. 1993Identification of a new interferon-alpha-inducible gene (p27) on human chromosome 14q32 and its expression in breast carcinoma.Cancer Res5340964101PubMedGoogle Scholar
  30. 30.
    Richterich, P 1998Estimation of errors in “raw” DNA sequences: a validation study.Genome Res8251259PubMedGoogle Scholar
  31. 31.
    Rollini, P, Fournier, REK 1997aA 370-kb cosmid contig of the serpin gene cluster on human chromosome 14q32.1: molecular linkage of the genes encoding alpha 1-antichymotrypsin, protein C inhibitor, kallistatin, alpha 1-antitrypsin, and corticosteroid-binding globulin.Genomics46409415Google Scholar
  32. 32.
    Rollini, P, Fournier, REK 1997bMolecular linkage of the human alpha 1-antitrypsin and corticosteroid-binding globulin genes on chromosome 14q32.1.Mamm Genome8913916Google Scholar
  33. 33.
    Rollini, P, Fournier, REK 1999Long-range chromatin reorganization of the human serpin gene cluster at 14q32.1 accompanies gene activation and extinction in microcell hybrids.Genomics562230CrossRefPubMedGoogle Scholar
  34. 34.
    Rollini, P, Fournier, REK 2000Differential regulation of gene activity and chromatin structure within the human serpin gene cluster at 14q32.1 in macrophage microcell hybrids.Nucleic Acids Res2817671777CrossRefPubMedGoogle Scholar
  35. 35.
    Rollini, P, Namciu, SJ, Marsden, MD, Fournier, REK 1999Identification and characterization of nuclear matrix-attachment regions in the human serpin gene cluster at 14q32.1.Nucleic Acids Res2737793791CrossRefPubMedGoogle Scholar
  36. 36.
    Rollini, P, Xu, L, Fournier, REK 2000Stable expression and cell-specific chromatin structure of human alpha 1-antitrypsin cosmid transgenes in rat hepatoma cells.Nucleic Acids Res2836053614CrossRefPubMedGoogle Scholar
  37. 37.
    Salamov, AA, Solovyev, VV 2000Ab initio gene finding in Drosophila genomic DNA.Genome Res10516522Google Scholar
  38. 38.
    Singh, GB, Kramer, JA, Krawetz, SA 1997Mathematical model to predict regions of chromatin attachment to the nuclear matrix.Nucleic Acids Res2514191425PubMedGoogle Scholar
  39. 39.
    Strausberg, RL, Feingold, EA, Grouse, LH, Darge, JG, Klausner, RD,  et al. 2002Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.Proc Nat Acad Sci USA991689916903CrossRefPubMedGoogle Scholar
  40. 40.
    Zhao, Y, Yu, L, Fu, Q, Chen, W, Jiang, J,  et al. 2000Cloning and characterization of human DDX24 and mouse Ddx24, two novel putative DEAD-Box proteins, and mapping DDX24 to human chromosome 14q32.Genomics67351355CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 2004

Authors and Affiliations

  • Stephanie J. Namciu
    • 1
  • Richard D. Friedman
    • 1
  • Mark D. Marsden
    • 1
  • Lourdes M. Sarausad
    • 1
  • Christine L. Jasoni
    • 1
  • R. E. K. Fournier
    • 1
  1. 1.Division of Basic SciencesFred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., A2-O25, Seattle, Washington 98109-1024USA

Personalised recommendations