Skip to main content
Log in

Molecular analysis of a recombinational hotspot adjacent to Lmp2 gene in the mouse MHC: Fine location and chromatin structure

  • Original Contribution
  • Published:
Mammalian Genome Aims and scope Submit manuscript

Abstract

Meiotic recombinations in the proximal region of the mouse major histocompatibility complex (MHC) are clustered within certain segments of chromosome, known as hotspots. In this study, we found that one of such hotspots, previously mapped between the Pb and Ob genes, is located very close to the 3′ end of the Lmp2 gene, which encodes a subunit of a proteolytic proteasome. To analyze the molecular basis of the site specificity of hotspots, we examined the structure of the chromatin around this Lmp2 hotspot and another one located in the MHC class II Eb gene, by monitoring DNase I-hypersensitive sites (DHSSs) of the chromatin. DHSSs were detected at the both hotspots in the somatic cells. In the meiotic cells, DHSS was detected within the Eb hotspot, as previously reported, but not in the Lmp2 hotspot. Thus, open structure of chromatin during meiosis, as monitored by hypersensitivity to DNase I, is not a general feature of mouse recombinational hotspots, contrasting the case of the lower eukaryote, S. cerevisiae, in which hotspots are always associated with DHSSs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Alt, F.W., Blackwell, T.K., Depinho, R.A., Reth, M.G., Yancopoulos, G.D. (1986). Regulation of genome rearrangement events during lymphocyte differentiation. Immunol. Rev. 89, 5–30.

    Article  PubMed  CAS  Google Scholar 

  • Bergman, Y., Rice, D., Grosschedl, R., Baltimore, D. (1984). Two regulatory elements for immunoglobulin k light chain gene expression. Proc. Natl. Acad. sci. USA 81, 5520–5524.

    Article  Google Scholar 

  • Bryda, E.C., DePari, J.A., Sant’;Angelo, D.B., Murphy, D.B., Passmore, H.C. (1992). Multiple sites of crossing over within the Eb recombinational hotspot in the mouse. Mamm. Genome 2, 123–129.

    Article  PubMed  CAS  Google Scholar 

  • Cao, L., Alani, E., Kleckner, N. (1990). A pathway for generation and processing of double-strand breaks during meiotic recombination in S. cerevisiae. Cell 61, 1089–1101.

    Article  PubMed  CAS  Google Scholar 

  • Cho, S., Attaya, M., Brown, M.G., Monaco, J.J. (1991). A cluster of transcribed sequences between the Pb and Ob genes of the murine major histocompatibility complex. Proc. Natl. Acad. sci. USA 88, 5197–5201.

    Article  PubMed  CAS  Google Scholar 

  • Church, G.M., Gilbert, W. (1984). Genomic sequencing. Proc. Natl. Acad. sci. USA 81, 1991–1995.

    Article  PubMed  CAS  Google Scholar 

  • Dietrich, W.F., Miller, J.C., Steen, R.G., Merchant, M., Damron, D., Nahf, R., Gross, A., Joyce, D.C., Wessel, M., Dredge, R.D., Marquis, A., Stein, L.D., Goodman, N., Page, D.C., Lander, E.S. (1994). A genetic map of the mouse with 4,006 simple sequence length polymorphisms. Nature Genet. 7, 220–245.

    Article  PubMed  CAS  Google Scholar 

  • Falkner, F.G., Zachau, H.G. (1984). Correct transcription of an immuno-globulin k gene requires an upstream fragment containing conserved sequence elements. Nature 310, 71–74.

    Article  PubMed  CAS  Google Scholar 

  • Feinberg, A.P., Vogelstein, B. (1984). A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal. Biochem. 137, 1266–1267.

    Google Scholar 

  • Fischer Lindahl, K. (1991). His and hers recombinational hotspots. Trends Genet. 7, 273–276.

    Article  Google Scholar 

  • Grabske, R.J., Lake, S., Gledhill, B.L., Meistrich,.L. (1975). Centrifugal elutriation: separation of spermatogenic cells on the basis of sedimentation velocity. J. Cell. Physiol. 86, 177–190.

    Article  PubMed  CAS  Google Scholar 

  • Grimm, C, Schaer, P., Munz, P., Kohli, J. (1991). The strong ADH1 promoter stimulates mitotic and meiotic recombination at the ADE6 gene of Schizosaccharomyces pombe. Mol. Cell. Biol. 11, 289–298.

    PubMed  CAS  Google Scholar 

  • Heine, D., Khambata, S., Wydner, K.S., Passmore, H.C. (1994). Analysis of recombinational hotspots associated with the p haplotype of the mouse MHC. Genomics 23, 168–177.

    Article  PubMed  CAS  Google Scholar 

  • Heinlein, U.A.O., Lange-Sablitzky, R., Schaal, H., Wille, W. (1986). Molecular characterization of the MT-family of dispersed middle-repetitive DNA in rodent genomes. Nucleic Acids Res. 14, 6403–6416.

    Article  PubMed  CAS  Google Scholar 

  • Henlkoff, S. (1984). Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing. Gene 28, 351–359.

    Article  Google Scholar 

  • Klein, J. (1975). Biology of the Mouse Histocompatibility-2 Complex. (New York: Springer-Verlag New York Inc).

    Google Scholar 

  • Kobori, J.A., Strauss, E., Minard, K., Hood, L. (1986). Molecular analysis of the hotspot of recombination in the murine histocompatibility complex. Science 234, 173–179.

    Article  PubMed  CAS  Google Scholar 

  • Lafuse, W.P., Berg, N., Savariayan, S., David, C.S. (1986). Mapping of a second recombination hotspot within the I-E region of the mouse H-2 gene complex. J. Exp. Med. 163, 1518–1528.

    Article  PubMed  CAS  Google Scholar 

  • Lafuse, W.P., Lee, S.T., David, C.S. (1990). Molecular analysis of two recombinant mouse strains with crossovers in the Ea recombination hot spot. J. Immunogenet. 17, 169–176.

    Article  PubMed  CAS  Google Scholar 

  • Lenardo, M.J., Baltimore, D. (1989). NF-kB: A pleiotropic mediator of inducible and tissue-specific gene control. Cell 58, 227–229.

    Article  PubMed  CAS  Google Scholar 

  • Ling, X., Shenkar, R., Sakai, D., Arnheim, N. (1993). The mouse Eb meiotic recombination hotspot contains a tissue-specific transcriptional enhancer. Immunogenetics 37, 331–336.

    Article  PubMed  CAS  Google Scholar 

  • Martinez, C.K., Monaco, J.J. (1991). Homology of proteasome subunits to a major histocompatibility complex-linked LMP gene. Nature 353, 664–667.

    Article  PubMed  CAS  Google Scholar 

  • Meistrich, M.L., Trostle, P.K. (1975). Separation of mouse testis cells by equilibrium density centrifugation in renografin gradients. Exp. Cell Res. 92, 231–244.

    Article  PubMed  CAS  Google Scholar 

  • Nicolas, A., Treco, Schultes, N.P., Szostak, J.W. (1989). An initiation site for meiotic gene conversion in the yeast Saccharomyces cerevisiae. Nature 338, 35–39.

    Article  PubMed  CAS  Google Scholar 

  • Ohta, K., Shibata, T., Nicolas, A. (1994). Changes in chromatin structure at recombination initiation sites during yeast meiosis. EMBO J. 13, 5754–5763.

    PubMed  CAS  Google Scholar 

  • Petes, T.D., Malone, R.E., Symington, L.S. (1991). Recombination in yeast. In The Molecular and Cellular Biology of the Yeast Saccharomyces: Genome Dynamics, Protein Synthesis, and Energetics, J.R. Broach, J.R. Pringle, E.W. Jones, eds. (Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press), pp. 407–521.

    Google Scholar 

  • Saha, B.K. (1993). Recruitment of multiple alleles within the Eb recombinational hotspot in murine MHC. Mamm. Genome 4, 565–570.

    Article  PubMed  CAS  Google Scholar 

  • Sambrook, J., Fritsch, E.F., Maniatis, T. (1989). Molecular Cloning: A Laboratory Manual. (Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press).

    Google Scholar 

  • Sanger, F., Nicklen, S., Coulson, A.R. (1977). DNA sequencing with chain-terminating inhibitors. Proc. Natl. Acad. sci. USA 74, 5463–5467.

    Article  PubMed  CAS  Google Scholar 

  • Sasaki, H., Jones, P.A., Chaillet, J.R., Fergunson-Smith, A.C., Barton, S.C., Reik, W., Surani, M.A. (1992). Parental imprinting: potentially active chromatin of the repressed maternal allele of the mouse insulin-like growth factor II (Igf2) gene. Genes & Dev. 6, 1843–1856.

    Article  CAS  Google Scholar 

  • Schultes, N.P., Szostak, J.W. (1991). A poly(dA • dT) tract is a component of the recombination initiation site at the ARG4 locus in Saccharomyces cerevisiae. Mol. Cell. Biol. 11, 322–328.

    PubMed  CAS  Google Scholar 

  • Shenkar, R., Shen, M., Arnheim, N. (1991). DNase I-hypersensitive sites and transcription factor-binding motifs within the mouse Eb meiotic recombination hot spot. Mol. Cell. Biol. 11, 1813–1819.

    PubMed  CAS  Google Scholar 

  • Shiroishi, T., Sagai, T., Moriwaki, K. (1982). A new wild-derived H-2 haplotype enhancing K-IA recombination. Nature 300, 370–372.

    Article  PubMed  CAS  Google Scholar 

  • Shiroishi, T., Sagai, T. Moriwaki, K. (1987). Sexual preference of meiotic recombination within the H-2 copmlex. Immunogenetics 25, 258–262.

    Article  PubMed  CAS  Google Scholar 

  • Shiroishi, T., Hanzawa, N., Sagai, T., Ishiura, M., Gojobori, T., Steinmetz, M., Moriwaki, K. (1990). Recombinational hotspot specific to female meiosis in the mouse major histocompatibility complex. Immunogenetics 31, 79–88.

    Article  PubMed  CAS  Google Scholar 

  • Shiroishi, T., Sagai, T., Hanzawa, N., Gotoh, H., Moriwaki, K. (1991). Genetic control of sex-dependent meiotic recombination in the major histocompatibility complex of the mouse. EMBO J. 10, 681–686.

    PubMed  CAS  Google Scholar 

  • Shiroishi, T., Sagai, T., Moriwaki, K. (1993). Hotspots of meiotic recombination in the mouse major histocompatibility complex. Genetica 88, 187–196.

    Article  PubMed  CAS  Google Scholar 

  • Steinmetz, M., Minard, K., Horvath, S., McNicholas, J., Srelinger, J., Wake, C, Long, E., Mach, B., Hood, L. (1982). A molecular map of the immune response region from the major histocompatibility complex of the mouse. Nature 300, 35–42.

    Article  PubMed  CAS  Google Scholar 

  • Steinmetz, M., Stephan, D., Fischer-Lindahl, K. (1986). Gene organization and recombinational hotspots in the murine major histocompatibility complex. Cell 44, 895–904.

    Article  PubMed  CAS  Google Scholar 

  • Sun, H., Treco, D., Schultes, N.P., Szostak, J.W. (1989). Double-strand breaks at an initiation site for meiotic gene conversion. Nature 338, 87–90.

    Article  PubMed  CAS  Google Scholar 

  • Uematsu, Y., Kiefer, H., Schulze, R., Fischer-Lindahl, K., Steinmetz, M. (1986). Molecular characterization of a meiotic recombinational hotspot enhancing homologous equal crossing-over. EMBO J. 5, 2123–2129.

    PubMed  CAS  Google Scholar 

  • Wang, A.M., Doyle, M.V., Mark, D.F. (1989). Quantitation of mRNA by the polymerase chain reaction. Proc. Natl. Acad. sci. USA 86, 9717–9721.

    Article  PubMed  CAS  Google Scholar 

  • White, M.A., Detloff, P., Strand, M., Petes, T.D. (1992). A promoter deletion reduces the rate of mitotic, but not meiotic, recombination at the HIS4 locus in yeast. Curr. Genet. 21, 109–116.

    Article  PubMed  CAS  Google Scholar 

  • Wu, C. (1989). Analysis of hypersensitive sites in chromatin. Methods Enzymol. 170 269–289.

    Article  PubMed  CAS  Google Scholar 

  • Wu, T.-C, Lichten, M. (1994). Meiosis-induced double-strand break sites determined by yeast chromatin structure. Science 263, 515–518.

    Article  PubMed  CAS  Google Scholar 

  • Zenvirth, D., Arbel, T., Sherman, A., Goldway, M., Klein, S., Simchen, G. (1992). Multiple sites for double-strand breaks in whole meiotic chromosomes of Saccharomyces cerevisiae. EMBO J. 11, 3441–3447.

    PubMed  CAS  Google Scholar 

  • Zhou, P., Cao, H., Smart, M., David, C. (1993). Molecular basis of genetic polymorphism in major histocompatibility complex-linked proteasome gene (Lmp2). Proc. Natl. Acad. sci. USA 90, 2681–2684.

    Article  PubMed  CAS  Google Scholar 

  • Zimmerer, E.J., Passmore, H.C. (1991). Structural and genetic properties of the Eb recombinational hotspot in the mouse. Immunogenetics 33, 132–140.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mizuno, K., Koide, T., Sagai, T. et al. Molecular analysis of a recombinational hotspot adjacent to Lmp2 gene in the mouse MHC: Fine location and chromatin structure. Mammalian Genome 7, 490–496 (1996). https://doi.org/10.1007/s003359900149

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s003359900149

Keywords

Navigation