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.
Similar content being viewed by others
References
GD Billingsley MA Walter GL Hammond DW Cox (1993) ArticleTitlePhysical 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 Gene 52 343–353 Occurrence Handle1:CAS:528:DyaK3sXktVaisbs%3D Occurrence Handle8381582
M Blum EM De Robertis T Kojis C Heinzmann I Klisak et al. (1994) ArticleTitleMolecular cloning of the human homeobox gene goosecoid (GSC) and mapping of the gene to human chromosome 14q32.1. Genomics 21 388–393 Occurrence Handle10.1006/geno.1994.1281 Occurrence Handle1:CAS:528:DyaK2MXhs1Ghug%3D%3D Occurrence Handle7916327
PL Broeker HB Super MJ Thirman H Pomykala Y Yonebayashi et al. (1996) ArticleTitleDistribution 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. Blood 87 1912–1922 Occurrence Handle1:STN:280:BymB3c3ltFE%3D Occurrence Handle8634439
C Burge S Karlin (1997) ArticleTitlePrediction of complete gene structures in human genomic DNA. J Mol Biol 268 78–94 Occurrence Handle10.1006/jmbi.1997.0951 Occurrence Handle1:CAS:528:DyaK2sXjtlSqtL4%3D Occurrence Handle9149143
RW Carrell PA Pemberton DR Boswell (1987) ArticleTitleThe serpins: evolution and adaptation in a family of protease inhibitors. Cold Spring Harbor Symp Quanti Biol 52 527–535 Occurrence Handle1:CAS:528:DyaL1cXlsVGisrg%3D
PN Cockerill WT Garrard (1986) ArticleTitleChromosomal loop anchorage of the kappa immunoglobulin gene occurs next to the enhancer in a region containing topoisomerase II sites. Cell 44 273–282 Occurrence Handle1:CAS:528:DyaL28XitF2qtLw%3D Occurrence Handle3002631
ES Dieken EM Epner S Fiering REK Fournier M Groudine (1996) ArticleTitleEfficient modification of human chromosomal alleles using recombination-proficient chicken/human microcell hybrids. Nature Genet 12 174–182 Occurrence Handle1:CAS:528:DyaK28XosFCmtA%3D%3D Occurrence Handle8563756
JK Frazer DG Jackson JP Gaillard M Lutter YJ Liu et al. (2000) ArticleTitleIdentification of centerin: a novel human germinal center B cell-restricted serpin. Europ J Immuno 30 3039–3048 Occurrence Handle10.1002/1521-4141(200010)30:10<3039::AID-IMMU3039>3.0.CO;2-H Occurrence Handle1:CAS:528:DC%2BD3cXnslKrsLY%3D
SM Gasser UK Laemmli (1986) ArticleTitleCohabitation of scaffold binding regions with upstream/enhancer elements of three developmentally regulated genes of D. melanogaster. Cell 46 521–530 Occurrence Handle1:CAS:528:DyaL28Xlt1yksbw%3D Occurrence Handle3015418
PG Gettins (2000) ArticleTitleKeeping the serpin machine running smoothly. Genome Res 10 1833–1835 Occurrence Handle10.1101/gr.168900 Occurrence Handle1:CAS:528:DC%2BD3MXptw%3D%3D Occurrence Handle11116079
GV Glazko IB Rogozin MV Glazkov (2001) ArticleTitleComparative study and prediction of DNA fragments associated with various elements of the nuclear matrix. Biochim Biophy Acta 1517 351–364 Occurrence Handle10.1016/S0167-4781(00)00297-9 Occurrence Handle1:CAS:528:DC%2BD3MXhtFentL0%3D
GL Hammond CL Smith DA Underhill (1991) ArticleTitleMolecular studies of corticosteroid binding globulin structure, biosynthesis and function. J Steroid Biochem Mol Biol 40 755–762 Occurrence Handle10.1016/0960-0760(91)90300-T Occurrence Handle1:CAS:528:DyaK38XhvVOitQ%3D%3D Occurrence Handle1958574
X Han ZF Huang R Fiehler GJ Broze Jr (1999) ArticleTitleThe protein Z-dependent protease inhibitor is a serpin. Biochemistry 38 11073–11078 Occurrence Handle10.1021/bi990641a Occurrence Handle1:CAS:528:DyaK1MXkvVCrsbs%3D Occurrence Handle10460162
X Han R Fiehler GJ Broze (2000) ArticleTitleCharacterization of the protein Z-dependent protease inhibitor. Blood 96 3049–3055 Occurrence Handle1:CAS:528:DC%2BD3cXnslGntrs%3D Occurrence Handle11049983
R Heilig R Eckenberg JL Petit N Fonknechten C Da Silva et al. (2003) ArticleTitleThe DNA sequence and analysis of human chromosome 14. Nature. 421 601–607 Occurrence Handle10.1038/nature01348 Occurrence Handle1:CAS:528:DC%2BD3sXovFKnug%3D%3D Occurrence Handle12508121
JA Irving RN Pike AM Lesk JC Whisstock (2000) ArticleTitlePhylogeny of the serpin superfamily: implications of patterns of amino acid conservation for structure and function. Genome Res 10 1845–l864 Occurrence Handle10.1101/gr.GR-1478R Occurrence Handle1:CAS:528:DC%2BD3MXhtVY%3D Occurrence Handle11116082
E Izaurralde J Mirkovitch UK Laemmli (1988) ArticleTitleInteraction of DNA with nuclear scaffolds in vitro. J Mol Biol 200 111–125 Occurrence Handle1:CAS:528:DyaL1cXhs1els7c%3D Occurrence Handle3132558
P Jackers N Clausse M Fernandez A Berti F Princen et al. (1996) ArticleTitleSeventeen copies of the human 37 kDa laminin receptor precursor/p40 ribosome-associated protein gene are processed pseudogenes arisen from retropositional events. Biochim Biophys Acta 1305 98–104 Occurrence Handle10.1016/0167-4781(95)00206-5 Occurrence Handle1:CAS:528:DyaK28XhsFOisLk%3D Occurrence Handle8605257
R Kellum SC Elgin (1998) ArticleTitleChromatin boundaries: punctuating the genome. Curr Biol 8 R521–R524 Occurrence Handle1:CAS:528:DyaK1cXks1Gisbw%3D Occurrence Handle9705921
WJ Kent CW Sugnet TS Furey KM Roskin TH Pringle et al. (2002) ArticleTitleThe human genome browser at UCSC. Genome Res 12 656–664
B Levy-Wilson C Fortier (1989) ArticleTitleThe 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 Chem 264 21196–21204 Occurrence Handle1:CAS:528:DyaK3cXhsl2k Occurrence Handle2592370
MD Marsden REK Fournier (2003) ArticleTitleChromosomal elements regulate gene activity and chromatin structure of the human serpin gene cluster at 14q32.1. Mol Cell Biol 23 3516–3526 Occurrence Handle10.1128/MCB.23.10.3516-3526.2003 Occurrence Handle1:CAS:528:DC%2BD3sXjs1yhtr4%3D Occurrence Handle12724410
CJ Marshall (1993) ArticleTitleEvolutionary relationships among the serpins. Phil Trans R Soc London—Ser B: Biol Sci 342 101–119 Occurrence Handle1:CAS:528:DyaK2cXlt1ynt7s%3D
J Mirkovitch ME Mirault UK Laemmli (1984) ArticleTitleOrganization of the higher-order chromatin loop: specific DNA attachment sites on nuclear scaffold. Cell 39 223–232 Occurrence Handle6091913
K Murakami T Takagi (1998) ArticleTitleGene recognition by combination of several gene-finding programs. Bioinformatics 4 665–675 Occurrence Handle10.1093/bioinformatics/14.8.665
T Nagase R Kikuno K Ishikawa M Hirosawa O Ohara (2000) ArticleTitlePrediction 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 Res 7 143–150 Occurrence Handle1:CAS:528:DC%2BD3cXjt1Gltrg%3D Occurrence Handle10819331
JR Paulson UK Laemmli (1977) ArticleTitleThe structure of histone-depleted metaphase chromosomes. Cell 12 817–828 Occurrence Handle1:CAS:528:DyaE1cXhslygsA%3D%3D Occurrence Handle922894
L Phi-Van WH Stratling (1996) ArticleTitleDissection of the ability of the chicken lysozyme gene 5′ matrix attachment region to stimulate transgene expression and to dampen position effects. Biochemistry 35 10735–10742 Occurrence Handle10.1021/bi9603783 Occurrence Handle1:CAS:528:DyaK28XksFOqsrs%3D Occurrence Handle8718863
UB Rasmussen C Wolf MG Mattei MP Chenard JP Bellocq et al. (1993) ArticleTitleIdentification of a new interferon-alpha-inducible gene (p27) on human chromosome 14q32 and its expression in breast carcinoma. Cancer Res 53 4096–4101 Occurrence Handle1:CAS:528:DyaK2cXhvVer Occurrence Handle8358738
P Richterich (1998) ArticleTitleEstimation of errors in “raw” DNA sequences: a validation study. Genome Res 8 251–259 Occurrence Handle1:CAS:528:DyaK1cXitlWksLk%3D Occurrence Handle9521928
P Rollini REK Fournier (1997a) ArticleTitleA 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. Genomics 46 409–415 Occurrence Handle1:CAS:528:DyaK1cXmt12hsg%3D%3D
P Rollini REK Fournier (1997b) ArticleTitleMolecular linkage of the human alpha 1-antitrypsin and corticosteroid-binding globulin genes on chromosome 14q32.1. Mamm Genome 8 913–916 Occurrence Handle1:CAS:528:DyaK2sXnvVyksb8%3D
P Rollini REK Fournier (1999) ArticleTitleLong-range chromatin reorganization of the human serpin gene cluster at 14q32.1 accompanies gene activation and extinction in microcell hybrids. Genomics 56 22–30 Occurrence Handle10.1006/geno.1998.5680 Occurrence Handle1:CAS:528:DyaK1MXht1Oqtr4%3D Occurrence Handle10036182
P Rollini REK Fournier (2000) ArticleTitleDifferential regulation of gene activity and chromatin structure within the human serpin gene cluster at 14q32.1 in macrophage microcell hybrids. Nucleic Acids Res 28 1767–1777 Occurrence Handle10.1093/nar/28.8.1767 Occurrence Handle1:CAS:528:DC%2BD3cXjtlKgs78%3D Occurrence Handle10734196
P Rollini SJ Namciu MD Marsden REK Fournier (1999) ArticleTitleIdentification and characterization of nuclear matrix-attachment regions in the human serpin gene cluster at 14q32.1. Nucleic Acids Res 27 3779–3791 Occurrence Handle10.1093/nar/27.19.3779 Occurrence Handle1:CAS:528:DyaK1MXms1Wrurs%3D Occurrence Handle10481016
P Rollini L Xu REK Fournier (2000) ArticleTitleStable expression and cell-specific chromatin structure of human alpha 1-antitrypsin cosmid transgenes in rat hepatoma cells. Nucleic Acids Res 28 3605–3614 Occurrence Handle10.1093/nar/28.18.3605 Occurrence Handle1:CAS:528:DC%2BD3cXmvVamtrs%3D Occurrence Handle10982883
AA Salamov VV Solovyev (2000) ArticleTitle Ab initio gene finding in Drosophila genomic DNA. Genome Res 10 516–522
GB Singh JA Kramer SA Krawetz (1997) ArticleTitleMathematical model to predict regions of chromatin attachment to the nuclear matrix. Nucleic Acids Res 25 1419–1425 Occurrence Handle1:CAS:528:DyaK2sXis1Sku7c%3D Occurrence Handle9060438
RL Strausberg EA Feingold LH Grouse JG Darge RD Klausner et al. (2002) ArticleTitleGeneration and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proc Nat Acad Sci USA 99 16899–16903 Occurrence Handle10.1073/pnas.242603899 Occurrence Handle12477932
Y Zhao L Yu Q Fu W Chen J Jiang et al. (2000) ArticleTitleCloning and characterization of human DDX24 and mouse Ddx24, two novel putative DEAD-Box proteins, and mapping DDX24 to human chromosome 14q32. Genomics 67 351–355 Occurrence Handle10.1006/geno.2000.6255 Occurrence Handle1:CAS:528:DC%2BD3cXlsVKluro%3D Occurrence Handle10936056
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Namciu, S.J., Friedman, R.D., Marsden, M.D. et al. Sequence organization and matrix attachment regions of the human serine protease inhibitor gene cluster at 14q32.1 . Mamm Genome 15, 162–178 (2004). https://doi.org/10.1007/s00335-003-2311-y
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s00335-003-2311-y