Skip to main content
Log in

Cloning and chromosome mapping of human retinoid X receptor β: selective amino acid sequence conservation of a nuclear hormone receptor in mammals

  • Original Investigations
  • Published:
Human Genetics Aims and scope Submit manuscript

Abstract

The murine retinoid X receptor β (mRXRβ) is a nuclear hormone receptor that activates transcription of murine major histocompatibility complex (MHC) class I genes in response to retinoic acid. In this study, the human RXRβ gene was mapped onto the short arm or centromeric region of chromosome 6 (6pter-q13), which also harbors the MHC. Chromosomal localization was performed by Southern hybridization of genomic DNA from human rodent cell hybrids with the mRXRβ gene as a probe. In addition, a full-length cDNA clone encoding a human RXRβ was isolated by nucleic acid screening of a human cDNA library with a fragment of the mRXRβ gene as a probe. Comparison of the nucleotide-coding sequences of the human and the murine RXRβ revealed a predominance of third base substitutions, resulting in selective conservation of the predicted amino acid sequence of the proteins. The overall sequence homology was 97.6% on the amino acid level as opposed to 91.6% on the nucleotide level. In Northern hybridization experiments with the human cDNA as a probe, RXRβ gene transcripts were detected in a variety of human tumor cell lines, regardless of whether these cell lines expressed MHC class I genes.

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

  • Beato M (1989) Gene regulation by steroid hormones. Cell 56:335–344

    Google Scholar 

  • DiSanto JP, Knowles RW, Flomenberg N, Dupont B (1988) The human Lyt-3 molecule requires CD8 for cell surface expression. EMBO J 7:3465–3470

    Google Scholar 

  • Fleischhauer K, Park JH, DiSanto JP, Marks MS, Ozato K, Yang SY (1992) Isolation of a full-length cDNA clone encoding a N-terminally variant form of the human retinoid X receptor β. Nucleic Acids Res 20:1801

    Google Scholar 

  • Forman BM, Samuels HH (1990) Interactions among a subfamily of nuclear hormone receptors: The regulatory zipper model. Mol Endocrinol 4:1293–1301

    Google Scholar 

  • Glass CK, Rosenfeld MG (1991) Regulation of gene transcription by thyroid hormones and retinoic acid. In: Foukes G, Cohen P (eds) Molecular aspects of cellular regulation: the hormonal control regulation of gene transcription. Elsevier, Amsterdam, pp 299–327

    Google Scholar 

  • Green S, Chambon P (1988) Nuclear receptors enhance our understanding of transcription regulation. Trends Genet 4:309–314

    Google Scholar 

  • Hamada K, Gleason SL, Levi BZ, Hirschfeld S, Appella E, Ozato K (1989) H-2RIIBP, a member of the nuclear hormone receptor superfamily that binds to both the regulatory element of major histocompatibility complex class I genes and the estrogen response element. Proc Natl Acad Sci USA 86:8289–8293

    Google Scholar 

  • Kliewer SA, Umesono K, Mangelsdorf DJ, Evans RM (1992) Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling. Nature 355:446–449

    Google Scholar 

  • Leid M. Kastner P, Lyons R, Nakshatri H, Saunders M, Zacharewski T, Chen JY, Staub A, Garnier JM, Mader S, Chambon P (1992) Purification, cloning, and RXR identity of the HeLa cell factor with which RAR or TR heterodimerizcs to bind target sequences efficiently. Cell 68:377–395

    Google Scholar 

  • Levin AA, Sturzenbecker LJ, Kazmer S, Bosakowski T, Huselton C, Allenby G, Speck J, Kratzeisen C, Rosenberger M, Lovey A, Grippo JF (1992) A 9-cis retinoic acid stereoisomer binds to and activates the nuclear receptor RXRα. Nature 355:359–361

    Article  CAS  PubMed  Google Scholar 

  • Lotan R (1980) Effects of vitamin A and its analogs (retinoids) on renal and neoplastic cells. Biochim Biophys Acta 605:33–91

    Google Scholar 

  • Mangelsdorf DJ, Ong ES, Dyck JA, Evans RM (1990) A nuclear receptor that identifies a novel retinoic acid response pathway. Nature 345:224–229

    Google Scholar 

  • Mangelsdorf DJ, Borgmcyer U, Heyman RA, Zhou JY, Ong ES, Oro AE, Kakizuka A, Evans RM (1992) Characterization of three RXR genes that mediate the action of 9-cis retinoic acid. Genes Dev 6:329–344

    Google Scholar 

  • Maniatis T, Fritsch EF, Sambrook J (1989) Molecular cloning: a laboratory manual, 2nd edn. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY

    Google Scholar 

  • Marks MS, Hallenbeck PL, Nagata T, Segars JH, Appella E, Nikodem VM, Ozato K (1992) 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

    Google Scholar 

  • McBride OW, Hieter P, Hollis GF, Swan DC, Otey M, Leder P (1982) Chromosomal location of human k and λ immunoglobulin light chain constant region genes. J Exp Med 155:1480–1490

    Google Scholar 

  • McBride OW, Swan DC, Tonick S, Gol R, Klamanis D, Moore D, Aaronson S (1983) Regional chromosomal localization of N-ras K-ras-1 K-ras-2 and myb oncogenes in human cells. Nucleic Acids Res 11:8221–8236

    Google Scholar 

  • McBride OW, Malini R, Hatfield D (1987) Opal suppressor phosphoserine tRNA gene and pseudogene are located on human chromosomes 19 and 22, respectively. J Biol Chem 262:11163–11166

    Google Scholar 

  • Nagata T, Segars JH, Levi BZ, Ozato K (1992) Retinoic acid-dependent transactivation of major histocompatibility complex class I promoters by the nuclear hormone receptor H-2 RIIBP in undifferentiated embryonal carcinoma cells. Proc Natl Acad Sci USA 89:937–941

    Google Scholar 

  • Oro AE, McKeown M, Evans RM (1990) Relationship between the product of the Drosophila ultraspiracle locus and the vertebrate retinoid X receptor. Nature 347:298–301

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Shea MJ, King DL, Conboy MJ, Mariani BD, Kafatos FC (1990) Proteins that bind to Drosophila chorion cis-regulatory elements: a new C2H2 zinc finger protein and a C2C2 steroid receptor-like component. Genes Dev 4:1128–1140

    Google Scholar 

  • Silverman T, Rein A, Orrison B, Langloss J, Bratthauer G, Miyazaki JI, Ozato K (1988) Establishment of cell lines from somite stage mouse embryos and expression of major histocompatibility class I genes in these cells. J Immunol 140:4378–4387

    Google Scholar 

  • Sporn MB, Roberts AB (1983) Role of retinoids in differentiation and carcinogenesis. Cancer Res 43:3034–3040

    Google Scholar 

  • Umesono K, Murakemi KK, Thompson CC, Evans RM (1991) Direct repeats as selective response elements for the thyroid hormone, retinoic acid, and vitamin D3 receptors. Cell 65:1255–1266

    Google Scholar 

  • Warrell RP, Frankel SR, Miller WH, Scheinberg DA, Itri LM, Hittelman WN, Vyas R, Andreef M, Tafuri A, Jakubowski A, Gabrilove J, Gordon MS, Dmitrovsky E (1991) Differentiation therapy of acute promyelocytic leukemia with tretinoin (alltrans-retinoic acid). N Engl J Med 324:1385–1393

    Google Scholar 

  • Yamamoto KR (1985) Steroid receptor regulated transcription of specific genes and gene networks. Annu Rev Genet 19:209–252

    Google Scholar 

  • Yu VC, Delsert C, Andersen B, Holloway JM, Devary OV, Näär AM, Kim SY, Boutin JM, Glass CK, Rosenfeld MG (1991) RXRβ: a coregulator that enhances binding of retinoic acid, thyroid hormone, and vitamin D receptors to their cognate response elements. Cell 67:1251–1266

    Google Scholar 

  • Zhang XK, Hoffmann B, Tran PBV, Graupner G, Pfahl M (1992) Retinoid X receptor is an auxiliary protein for thyroid hormone and retoic acid receptors. Nature 355:441–446

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fleischhauer, K., McBride, O.W., DiSanto, J.P. et al. 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 (1993). https://doi.org/10.1007/BF00217449

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00217449

Keywords

Navigation