, Volume 41, Issue 2–3, pp 83–90 | Cite as

Physical mapping of the retinoid X receptorB gene in mouse and human

  • Toshi Nagata
  • Elizabeth H. Weiss
  • Kuniya Abe
  • Kyoko Kitagawa
  • Asako Ando
  • Yukie Yara-Kikuti
  • Michael F. Seldin
  • Keiko Ozato
  • Hidetoshi Inoko
  • Makoto Taketo
Original Paper


Retinoid X receptors (RXRs) are zinc finger-containing nuclear transcription factors. They belong to the nuclear receptor superfamily that contains retinoid receptors, vitamin D receptors, thyroid hormone receptors, and steroid hormone receptors as well as the so-called orphan receptors. We previously mapped all three RXR genes on mouse chromosomes, using a panel of Mus spretus-Mus musculus interspecific backcross mice: Namely, the RXRA- gene (Rxra) on Chr 2 near the centromere, the RXRB gene (Rxrb) on Chr 17 in the H2 region, and the RXRG gene (Rxrg) on distal Chr 1. Using cosmid clones that cover the major histocompatibility complex (MHC) region, we determined the precise physical map positions of the gene encoding mouse and human RXRB, respectively. The mouse gene (Rxrb) maps between H2-Ke4 and H2-Ke5: namely, immediately telomeric to H2-Ke4 which encodes a histidine-rich transmembrane protein, and 12 kilobases centromeric to H2-Ke5 which is expressed in lymphoid tissues. Rxrb and H2-Ke4 are transcribed into opposite directions from a CpG-rich promoter of about 250 base pairs. This gene organization is well conserved also in the human genome at the HLA-DP subregion of CHr 6p, underscoring the strong conservation of the gene organization in the MHC region between the two mammals.


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  1. Abe, K., Wei, J.-G., Wei, F.-S., Hsu, Y.-C., Uehara, H., Artzt, K., and Bennett, D. Searching for coding sequences in the mammalian genome: the H-2K region of the mouse MHC is replete with genes expressed in embryos. EMBO J 7: 3441–3449, 1988Google Scholar
  2. Allenby, G., Bocquel, M.-T., Saunders, M., Kazmer, S., Speck, J., Rosenberger, M., Lovey, A., Kastner, P., Grippo, J. F., Chambon, P., and Levin, A. A. Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids. Proc Natl Acad Sci USA 90: 30–34, 1993PubMedGoogle Scholar
  3. Almasan, A., Mangelsdorf, D. J., Ong, E. S., Wahl, G. M., and Evans, R. M. Chromosomal localization of the human retinoid X receptors. Genomics 20: 397–403, 1994Google Scholar
  4. Artzt, K., Abe, K., Uehara, H., and Bennett, D. Intra-H-2 recombination in t haplotypes shows a hot spot and close linkage of l tw5 to H-2K. Immunogenetics 28: 30–37, 1988Google Scholar
  5. Ausubel, F. M., Brent, R., Kingston, R. E., Moore, D. D., and Smith, J. A. Current Protocols in Molecular Biology, Wiley Interscience, Brooklyn, 1986Google Scholar
  6. Aziz, N., Maxwell, M. M., St.-Jacques, B., and Brenner, B. M. Downregulation of Ke6, a novel gene encoded within the major histocompatibility complex, in murine polycystic kidney disease. Mol Cell Biol 13: 1847–1853, 1993 aGoogle Scholar
  7. Aziz, N., Maxwell, M. M., St.-Jacques, B., and Brenner, B. M. Downregulation of Ke 6, a novel gene encoded within the major histocompatibility complex, in murine polycystic kidney disease. Mol Cell Biol 13: 6614 [Erratum], 1993 bGoogle Scholar
  8. Bird, A. P. CpG-rich-islands and the function of DNA methylation. Nature 321: 209–213, 1986Google Scholar
  9. Blumberg, B., Mangelsdorf, D. J., Dyck, J. A., Bittner, D. A., Evans, R. M., and De Robertis, E. M. Multiple retinoid-responsive receptors in a single cell: families of retinoid “X” receptors and retinoic acid receptors in the Xenopus egg. Proc Natl Acad Sci USA 89: 2321–2325, 1992Google Scholar
  10. Brockes, J. Reading the retinoid signals. Nature 345: 766–768, 1990Google Scholar
  11. Bugge, T. H., Pohl, J., Lonnoy, O., and Stunnenberg, H. G. RXRα, a promiscous partner of retinoic acid and thyroid hormone receptors. EMBO J 11: 1409–1418, 1992Google Scholar
  12. De Luca, M.. Retinoids and their receptors in differtiation, embryogenesis, and neoplasia. FASEB J 5: 2924–2933 1991Google Scholar
  13. Ebersole, T., Lai, F., and Artzt, K. New molecular markers for the distal end of the t-complex and their relationships to mutations affecting mouse development. Gennetics 131: 175–182, 1992Google Scholar
  14. Fitzgibbon, J., Gillett, G. T., Woodward, K. J., Boyle, J. M., Wolfe, J., and Povey, S. Mapping of RXRB to human chromosome 6p21.3. Ann Hum Genet 57: 203–209, 1993Google Scholar
  15. Fleischhauer, K., McBride, O. W., DiSanto, J. P., Ozato, K., and Yang, S. Y. Cloning and chromosome mapping of human retinoid X receptor β: selective amino acid sequence conservation of a nuclear hormone receptor in mammals. Hum Genet 90: 505–510, 1993Google Scholar
  16. Grosveld, F. G., Lund, T., Murray, E. J., Mellor, A. L., Dahl, H. H. M., and Flavell, R. A. The construction of cosmid libraries which can be used to transform eukaryotic cells. Nucleic Acids Res 10: 6715–6732, 1982Google Scholar
  17. Hallenbeck, P. L., Marks, M. S., Lippoldt, R. E., Ozato, K., and Nikodem, V. M. Heterodimerization of thyroid hormone (TH) receptor with H-2RIIBP (RXRβ) enhances DNA binding and TH-dependent transcriptional activation. Proc Natl Acad Sci USA 89: 5572–5576, 1992Google Scholar
  18. Hamada, K., Gleason, S. L., Levi, B.-Z., Hirschfeld, S., Appella, E., and Ozato, K. H-2RIIBP, a member of the nuclear hormone receptor superfamily that binds to both the regulatory element of major histocompatibility class I genes and the estrogen response element. Proc Natl Acad Sci USA 86: 8289–8293, 1989Google Scholar
  19. Hamazato, F., Fujimura, Y., Tamai, Y., Takemoto, Y., Matsushiro, A., and Nozaki, M. Sequence specific binding of Ets-1 to the mouse cytokeratin EndoA gene enhancer. Biochem Biophys Res Comm 192: 430–438, 1993Google Scholar
  20. Hanson, I. M. and Trowsdale, J. Colinearity of novel genes in the class Ii regions of the MHC in mouse and human. Immunogenetics 34: 5–11, 1991Google Scholar
  21. Heyman, R. A., Mangelsdorf, D. J., Dyck, J. A., Stein, R. B., Eichele, G., Evans, R. M., and Thaller, C. 9-Cis retinoic acid is a high affinity ligand for the retinoid X receptor. Cell 68: 397–406, 1992CrossRefPubMedGoogle Scholar
  22. Himmelbauer, H., Artzt, K., Barlow, D., Fischer-Lindahl, K., Lyon, M., Klein, J., and Silver, L. M. Mouse chromosome 17. Mammalian Genome 4: S230-S252, 1993Google Scholar
  23. Hoopes, C. W., Taketo, M., Ozato, K., Liu, Q., Howard, T. A., Linney, E., and Seldin, M. F. Mapping of the mouse Rxr loci encoding nuclear retinoid X receptors RXRα, RXRβ, and RXRγ. Genomics 14: 611–617, 1992Google Scholar
  24. Ishikawa, T., Umesono, K., Mangelsdorf, D. J., Aburatani, H., Stanger, B. Z., Shibasaki, Y., Imawari, M., Evans, R. M., and Takaku, F. A functional retinoic acid receptor encoded by the gene on human chromosome 12. Mol Endocrinol 4: 837–844, 1990Google Scholar
  25. Janatipour, M., Naumov, Y., Sugimura, K., Okamoto, N., Tsuji, K., Abe, K., and Inoko, H. Search for MHC-associated genes in human: five new genes centromeric to HLA-DP with yet unknown functions. Immunogenetics 35: 272–278, 1992Google Scholar
  26. Kliewer, S. A., Umesono, K., Heyman, R. A., Mangelsdorf, D. J., Dyck, J. A., and Evans, R. M. Retinoid X receptor-COUP-TF interactions modulate retinoic acid signaling. Proc Natl Acad Sci USA 89: 1448–1452, 1992 aGoogle Scholar
  27. Kliewer, S. A., Umesono, K., Mangelsdorf, D. J., and Evans, R. M. Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling. Nature 355 446–449, 1992 bGoogle Scholar
  28. Kliewer, S. A., Umesono, K., Noonan, D. J., Heyman, R. A., and Evans, R. M. Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptors. Nature 358: 771–774, 1992 cGoogle Scholar
  29. Leid, M., Kastner, P., and Chambon, P. Multiplicity generates diversity in the retinoic acid signalling pathways. Trends Biochem Sci 17: 427–433, 1992 aGoogle Scholar
  30. Leid, M., Kastner, P., Lyons, R., Nakshatri, H., Saunders, M., Zacharewski, T., Chen, J.-Y., Staub, A., Garnier, J.-M., Mader, S., and Chambon, P. Purification, cloning and RXR identity of the HeLa cell factor with which RAR or TR heterodimerizes to bind target sequences efficiently. Cell 68: 377–395, 1992 bGoogle Scholar
  31. Levin, A. A., Sturzenbecker, L. J., Kazmer, S., Bosakowski, T., Huselton, C., Allenby, G., Speck, J., Kratzeisen, Cl., Rosenberber, M., Lovey, A., and Grippo, J. F. 9-Cis retinoic acid stereo-isomer binds and activates the nuclear receptor RXRα. Nature 355: 359–361, 1992CrossRefPubMedGoogle Scholar
  32. Liu, Q. and Linney, E. The mouse retinoid-X receptor-γ gene: genomic organization and evidence for functional isoforms. Mol Endocrinol 7: 651–658, 1993Google Scholar
  33. Magnuson, T., Epstein, C. J., Silver, L. M., and Martin, G. R. Pluripotent embryonic stem cell lines can be derived from t w5/t w5 blastocysts. Nature 298: 750–753, 1982Google Scholar
  34. Mangelsdorf, D. J., Ong, E. S., Dyck, J. A., and Evans, R. M. Nuclear receptor that identifies a novel retinoic acid response pathway. Nature 345: 224–229, 1990Google Scholar
  35. Mangelsdorf, D. J., Borgmeyer, U., Heyman, R. A., Zhou, J. Y., Ong, E. S., Oro, A. E., Kakizuka, A., and Evans, R. M. Characterization of three RXR genes that mediate the action of 9-cis retinoic acid. Genes Devel 6: 329–344, 1992Google Scholar
  36. Marks, M. S., Hallenbeck, P. L., Nagata, T., Segars, J. H., Appella, E., Nikodem, V. M., and Ozato, K. H-2RIIBP (RXRβ) heterodimerization provides a mechanism for combinatorial diversity in the regulation of retinoic acid and thyroid hormone responsive genes. EMBO J 11: 1419–1435, 1992Google Scholar
  37. Mattèi, M.-G., de Thé, H., Mattèi, J.-F., Marchio, A., Tiollais, P., and Dejean, A. Assignment of the human hap retinoic acid receptor RARβ gene to the p24 band of chromosome 3. Hum Genet 80: 189–190, 1988 aGoogle Scholar
  38. Mattèi, M.-G., Petkovich, M., Mattèi, J.-F., Brand, N., and Chambon, P. Mapping of the human retinoic acid receptor to the q21 band of chromosome 17. Hum Genet 80: 186–188, 1988 bGoogle Scholar
  39. Nadeau, J. H., Davisson, M. T., Doolitle, D. P., Grant, P., Hillyard, A. L., Kosowsky, M., and Roderick, T. H. Comparative map for mice and humans. Mammalian Genome 1: S461-S515, 1991Google Scholar
  40. Nadeau, J. H., Compton, J. G., Giguère, V., Rossant, J., and Varmuza, S. Close linkage of retinoic acid receptor genes with homeobox-and keratin-encoding genes on paralogous segments of mouse chromosome 11 and 15. Mammalian Genome 3: 202–208,1992Google Scholar
  41. Nagata, T., Segars, J. H., Levi, B.-Z., and Ozato, K. Retinoic acid-dependent transactivation of major histocompatibility complex class I promoters by the nuclear hormone receptor H-2RIIBP in undifferentiated embryonal carcinoma cells. Proc Natl Acad Sci USA 89: 937–941, 1992Google Scholar
  42. Nagata, T., Kanno, Y., Ozato, K., and Taketo, M. The mouse Rxrb gene encoding RXRβ: genomic organization and two mRNA isoforms generated by alternative splicing of transcripts initiated from CpG island promoters. Gene 142: 183–189, 1994Google Scholar
  43. Nordeen, S. K. Luciferase reporter gene vectors for analysis of promoters and enhancers. Biotechniques 6: 454–457,1988Google Scholar
  44. Rowe, A., Eager, N. S. C., Brickell, P. M. A member of the RXR nuclear receptor family is expressed in neutral-crest-derived cells of the developing chick peripheral nervous system. Development 111: 771–778, 1991Google Scholar
  45. Sambrook, J., Fritsch, E. F., and Maniatis, T. Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, Cold Spring Harbor, 1989Google Scholar
  46. St.-Jacques, B., Han, T. H., MacMurray, A., and Shin, H.-S. A putative transmembrane protein with histidine-rich charge clusters encoded in the H-2K/t w5 region of mice. Mol Cell Biol 10: 138–145, 1990Google Scholar
  47. Taketo, M., Howard, T. A., and Seldin, M. F. Mapping of recombinant retrovirus integration sites that cause expression of the viral genome in murine embryonal carcinoma cells. Mammalian Genome 2: 240–245, 1992Google Scholar
  48. Taketo, M., Hoopes, C. W., Howard, T. A., Linney, E., and Seldin, M. F. Mapping of the mouse Rar loci encoding retinoic acid receptors RARα, RARβ and RARγ. Jpn J Genet 68: 175–184, 1993Google Scholar
  49. Wahl, G. M., Lewis, K. A., Ruiz, J. C., Rothenberg, B., Zhao, J., and Evans, G. A. Cosmid vectors for rapid genomic walking, restriction mapping, and gene transfer. Proc Natl Acad Sci USA 84: 2160–2164, 1987Google Scholar
  50. Weiss, E. H., Mellor, A., Golden, L., Fahrner, K., Simpson, E., Hurst, J., and Flavell, R. A. The structure of a mutant H-2 gene suggests that the generation of polymorphism in H-2 genes may occur by gene conversion-like events. Nature 301: 671–674, 1983Google Scholar
  51. Weiss, E. H., Golden, L., Fahrner, K., Mellor, A. L., Devlin, J. J., Bullman, H., Tiddens, H., Bud, H., and Flavell, R. A. Organization and evolution of the class I gene family in the major histocompatibility complex of the C57BL/10 mouse. Nature 310: 650–655, 1984Google Scholar
  52. Yeom, Y. I., Abe, K., Bennet, D., and Artzt, K. Testis-/embryo-expressed genes are clustered in the mouse H-2K region. Proc Natl Acad Sci USA 89: 773–777, 1992Google Scholar
  53. Yu, V. C., Delsert, C., Andersen, B., Holloway, J. M., Devary, O. V., Näär, A. M., Kim, S. Y., Boutin, J.-M., Glass, C. K., and Rosenfeld, M. G.: RXRβ: a coregulator that enhances binding of retinoic acid, thyroid hormone, and vitamin D receptors to their cognate response elements. Cell 67: 1251–1266, 1991Google Scholar
  54. Zhang, X.-K., Hoffmann, B., Tran, P. B.-V., Graupner, G., and Pfahl, M. Retinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors. Nature 355: 441–446, 1992Google Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Toshi Nagata
    • 1
  • Elizabeth H. Weiss
    • 2
  • Kuniya Abe
    • 3
  • Kyoko Kitagawa
    • 1
  • Asako Ando
    • 4
  • Yukie Yara-Kikuti
    • 4
  • Michael F. Seldin
    • 5
  • Keiko Ozato
    • 6
  • Hidetoshi Inoko
    • 4
  • Makoto Taketo
    • 1
  1. 1.Banyu Tsukuba Research Institute (Merck)TsukubaJapan
  2. 2.Institute for Anthropology and Human Genetics of Ludwig-Maximilians-UniversityMunichGermany
  3. 3.Institute of Molecular Embryology and GeneticsKumamoto University School of MedicineKumamotoJapan
  4. 4.Division of Molecular Life Science, Department of Genetic InformationTokai University Scholl of MedicineIseharaJapan
  5. 5.Department of Medicine and MicrobiologyDuke University Medical CenterDurnhamUSA
  6. 6.Laboratory of Molecular Growth RegualtionNational Institute of Child Health and Human Development, National Institutes of HealthBethesdaUSA

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