Abstract
A meiotic recombination hotspot exists within the second intron of the mouse major histocompatibility complex (MHC) gene, Eb. In the present study, a small fragment from the intron which contains two potential transcriptional regulatory elements was cloned into an expression vector and its effect on transcription was tested. This fragment was found to contain tissue-specific transcriptional enhancer activity. An octamer-like sequence and a B motif may contribute to this enhancer activity. Similar regulatory sequences with the same orientation and distance from one another are found in another mouse MHC recombination hotspot.
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Baldwin, A. S., Jr. and Sharp, P. A. Binding of a nuclear factor to a regulatory sequence in the promoter of the mouse H-2K b class I major histocompatibility gene. Mol Cell Biol 7: 305–313, 1987
Baldwin, A. S., Jr. and Sharp, P. A. Two transcription factors, NF-kB and H2TF1, interact with a single regulatory sequence in the class I major histocompatibility complex promoter. Proc Natl Acad Sci USA 85: 723–727, 1988
Begovich, A. B. and Jones, P. P. Free la Ea chain expression in the Ea +:Eb − recombinant strain A. TRF5. Immunogenetics 22: 523–532, 1985
Benoist, C. and Mathis, D. Regulation of major histocompatibility complex class II genes: X, Y and other letters of the Alphabet. Annu Rev Immunol 8: 681–715, 1990
Blackwell, T. K., Moore, M. W., Yancopoulos, G. D., Suh, H., Lutzker, S., Selsing, E., and Alt, F. W. Recombination between Immunoglobulin variable region gene segment is enhanced by transcription. Nature 324: 585–589, 1986
Blackwell, T. K. and Alt, F. W. Molecular characterization of the lymphoid V(D)J recombination activity. J Biol Chem 264: 10327–10330, 1989
Bryda, E. C., DePari, J. A., Sant'Angelo, D. B., Murphy, D. B., and Passmore, H. C. Multiple sites of crossing over within the Eβ recombinational hotspot in the mouse. Mammalian Genome 2: 123–129, 1992
DeFranco, D. and Yamamoto, K. R. Two different factors act separately or together to specify functionally distinct activities at a single transcriptional enhancer. Mol Cell Biol 6: 993–1001, 1986
Dorn, A., Durand, B., Marfing, C., LeMeur, M., Benoist, C., and Mathis, D. Conserved major histocompatibility complex class II boxes-X and-Y are transcriptional control elements and specifically bind nuclearproteins. Proc Natl Acad Sci USA 84: 6249–6253, 1987
Felgner, P. L., Gadek, T. R., Holm, M., Roman, R., Chan, H. W., Wenz, M., Northrop, J. P., Ringold, G. M., and Danielsen, M. Lipofection: A highly efficient, lipid-mediated-DNA-transfection procedure. Proc Natl Acad Sci USA 84: 7413–7417, 1987
Finn, P. W., Kara, C. J., Van, T. T., Douhan, J., Boothby, M. R., and Glimcher, L. H. The presence of a DNA binding complex correlates with Eβ class II MHC gene expression. EMBO J 9: 1543–1549, 1990a
Finn, P. W., Kara, C. J., Douhan, J. D., Van, T. T., Folsom, V., and Glimcher, L. H. Interferon γ regulates binding of two nuclear protein complexes in a macrophage cell line. Proc Natl Acad Sci USA 87: 914–918, 1990b
Gorman, C. M., Moffat, L. F., and Howard, B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol 2: 1044–1051, 1982
Gross, D. S. and Garrard, W. T. Nuclease hypersensitive sites in chromatin. Annu Rev Biochem 57: 159–197, 1988
Kawasaki, E. S. Amplification of RNA. In M. A. Innis, D. H. Gelfand, J. J. Sninsky, and T. J. White (eds.): PCR Protocols: A Guide to Methods and Applications, pp. 27–27, Academic Press, San Diego, 1990
Kemler, I., Schreiber, E., Mueller, M. M., Matthias, P., and Schaffner, W. Octmer transcription factors bind to two different sequence motifs of the immunoglobulin heavy chain promoter. EMBO J 8: 2001–2008, 1989
Kemler, I., Bucher, E., Seipel, K., Muller-Immerglueck, M. M., and Schaffner, W. Promoter with the octamer DNA motif (ATG-CAAAT) can be ubiquitous or cell type-specific depending on binding affinity of the octamer site and Oct-factor concentration. Nucleic Acids Res 19: 237–242, 1991
Kobori, J. A., Straus, E., Minard, K., and Hood, L. Molecular analysis of the hotspot of recombination in murine major histocompatibility complex. Science 234: 173–179, 1986
Koch, W., Candeias, S., Guardiola, J., Accolla, R., Benoist, C., and Mathis, D. An enhancer factor defect in a mutant Burkitt lymphoma cell line. J Exp Med 167: 1781–1790, 1988
Koch, W., Benoist, C., and Mathis, D. Anatomy of a new B-cell-specific enhancer. Mol cell Biol 9: 303–311, 1989
Krimpenfort, P., Jong, R., Uematsu, Y., Dembic, Z., Ryser, S., Boehmer, H., Steinmetz, M., and Berns, A. Transcription of T-cell receptor beta-chain genes is controlled by a downstream regulatory element. EMBO J 7: 745–750, 1988
Lefranc, G. and Lefranc, M. P. Regulation of the immunoglobulin gene transcription. Biochemie 72: 7–17, 1990
Lenardo, M. J. and Baltimore, D. NF-KB: a pleiotropic mediator of inducible and tissue-specific gene control. Cell 58: 227–229, 1989
Maeda, H., Araki, K., Kitamura, D., Wong, J., and Watanabe, T. Nuclear factors binding to the human immunoglobulin heavy-chain gene enhancer. Nucleic Acids Res 15: 2851–2869, 1987
Martinez, C. K. and Monaco, J. J. Homology of proteasome subunits to a major histocompatibility complex-linked LMP gene. Nature 353: 664–667, 1991
Nicolas, A., Treco, D., Schultes, N. P., and Szostak, J. W. An initiation site for meiotic gene conversion in the yeast Saccharomyces cerevisiae. Nature 338: 35–39, 1989
Picard, D. and Yamamoto, K. R. Two signals mediate hormone-dependent nuclear localization of the glucocorticoid receptor. EMBO J 6: 3333–3340, 1987
Pierce, J. W., Lenardo, M., and Baltimore, D. Oligonucleotide that binds nuclear factor NF-kB acts as a lymphoid specific and inducible enhancer element. Proc Natl Acad Sci USA 85: 1482–1486, 1988
Ponticelli, A. S. and Smith, G. R. Chromosomal context dependence of a eukaryotic recombinational hotspot. Proc Natl Acad Sci USA 89: 227–231, 1992
Saha, B. K. and Cullen, S. E. Molecular mapping of murine I region recombinants: crossing over in the Eβ gene. J Immunol 136: 1112–1116, 1986
Saito, H., Maki, R. A., Clayton, L. K., and Tonegawa, S. Complete primary structures of the Eβ chain and gene of the mouse major histocompatibility complex. Proc Natl Acad Sci USA 80: 5520–5524, 1983
Saiki, R. K., Bugawan, T. L., Horn, G. T., Mullis, K. B., and Erlich, H. A. Analysis of enzymatically amplified β-globin and HLA-DQα DNA with allele-specific oligonucleotide probes. Nature 324: 163–166, 1986
Sakurai, M. and Strominger, J. L. B-cell specific enhancer activity of conserved upstream elements of the class II major histocompatibility complex DQB gene. Proc Natl Acad Sci USA 85: 6909–6913, 1988
Schuchert, P., Langsford, M., Kaslin, E., and Kohli, J. A specific DNA sequence is required for high frequency of recombination in the ade6 gene of fission yeast. EMBO J 10: 2157–2163, 1991
Schultes, N. P. and Szostak, J. W. A poly (dA ·dT) tract is a component of the recombination initiation site at the ARG4 locus in yeast. Mol Cell Biol 11: 322–328, 1991
Sen, R. and Baltimore, D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell 46: 705–716, 1986
Shenkar, R., Shen, M., and Arnheim, N. DNase I hypersensitive site and transcription factor binding motifs within the mouse Eβ meiotic recombination hotspot. Mol Cell Biol 11: 1813–1819, 1991
Sherman, P. A., Basta, P. V., Moore, T. L., Brown, A. M., and Ting, J. P-Y. Class II box consensus sequences in the HLA-DRα gene: transcriptional function and interaction with nuclear proteins. Mol Cell Biol 9: 50–56, 1989 a
Sherman, P. A., Basta, P. V., Heguy, A., Wloch, M. K., Roeder, R. G., and Ting, J. P-Y. The octamer motif is a B-lymphocyte specific regulatory element of the HLA-DRα gene promoter. Proc Natl Acad Sci USA 86: 6739–6743, 1989 b
Shiroishi, T., Hanzawa, N., Sagai, T., Ishiura, M., Gojobori, T., Steinmetz, M., and Moriwaki, K. Recombinational hotspot specific to female meiosis in the mouse major histocompatibility complex. Immunogenetics 31: 79–88, 1990
Shiroishi, T., Sagai, T., Hanzawa, N., Goatoh, H., and Moriwaki, K. Genetic control of sex-dependent meiotic recombination in the major histocompatibility complex of the mouse. EMBO J 10: 681–686, 1991
Steinmetz, M., Minard, K., Horvath, S., McNicholas, J., Srelinger, J., Wake, C., Long, E., Mach, B., and Hood, L. A molecular map of the immune response region from the major histocompatibility complex of the mouse. Nature 300: 35–42, 1982
Sullivan, K. E. and Peterlin, B. M. Transcriptional enhancers in the HLA-DQ subregion. Mol Cell Biol 7: 3315–3319, 1987
Thomas, B. J. and Rothstein, R. Elevated recombination rates in transcriptionally active DNA.Cell 56: 619–630, 1989
Thuriaux, P. Is recombination confined to structural genes on the eukaryotic genome? Nature 268: 460–462, 1977
Uematsu, Y., Kiefer, H., Schulze, R., Fischer-Lindahl, K., and Steinmetz, M. Molecular characterization of a meiotic recombinational hotspot enhancing homologous equal crossing-over. EMBO J 5: 2123–2129, 1986
Voelkel-Meiman, K., Keil, R. L., and Roeder, G. S. Recombination stimulating sequences in yeast ribosomal DNA correspond to sequences regulating transcription by RNA polymerase I. Cell 48: 1071–1079, 1987
Wang, Y., Larsen, A. S., and Peterlin, B. M. A tissue-specific transcriptional enhancer is found in the body of the HLA-DRα gene. J Exp Med 166: 625–636, 1987
Wildera, G. and Flavell, R. A. The nucleotide sequence of the murine I-Eb b immune response gene: evidence for gene conversion events in class II genes of the major histocompatibility complex. EMBO J 3: 1221–1225, 1984
Zabel, U., Schreck, R., and Baeuerle, P. A. DNA binding of purified transcription factor NF-kB. affinity, specificity, Zn2+ dependence, and differential half-site recognition. J Biol Chem 266: 252–260, 1991
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Correspondence to: N. Arnheim.
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Ling, X., Shenkar, R., Sakai, D. et al. The mouse Eb meiotic recombination hotspot contains a tissue-specific transcriptional enhancer. Immunogenetics 37, 331–336 (1993). https://doi.org/10.1007/BF00216797
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DOI: https://doi.org/10.1007/BF00216797