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PMID: 8093325 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Identification of a retinoic acid response element upstream of the murine Hox-4.2 gene.

Molecular and cellular biology ·Vol. 13 ·No. 1 ·1993-01-00 ·Pages 257-65

Pöpperl H, Featherstone MS

Abstract

Hox genes play an important role in the process of vertebrate pattern formation, and their expression is intricately regulated both temporally and spatially. All-trans-retinoic acid (RA), a physiologically active metabolite of vitamin A, affects the expression of a large number of Hox genes in vitro and in vivo. However, the regulatory mechanisms underlying the RA response of these genes have not been extensively studied, and no response element for RA receptors (RARs) has been characterized in a Hox regulatory region. The expression of murine Hox-4.2 and its human homolog, HOX4B, is increased in embryonal carcinoma (EC) cell lines upon RA treatment (M. S. Featherstone, A. Baron, S. J. Gaunt, M.-G. Mattei, and D. Duboule, Proc. Natl. Acad. Sci. USA 85:4760-4764, 1988; A. Simeone, D. Acampora, V. Nigro, A. Faiella, M. D'Esposito, A. Stornaiuolo, F. Mavilio, and E. Boncinelli, Mech. Dev. 33:215-228, 1991). Using transient expression assays, we showed that luciferase reporter gene constructs carrying genomic sequences located upstream of Hox-4.2 responded to RA in murine P19 EC cells. A 402-bp NcoI fragment was necessary for the RA responsiveness of reporter constructs. This fragment contained a regulatory element, 5'-AGGTGA(N)5AGGTCA-3', that closely resembles the consensus sequence for an RA response element. The Hox-4.2 RA response element was critical for the RA induction and specifically bound RARs. In addition, the response to RA could be inhibited by expressing a dominant negative form of RAR alpha in transfected P19 EC cells. These results suggested that Hox-4.2 is a target for RAR-mediated regulation by RA.

Related Genes
Hox-4.2
MeSH Terms
Animals Base Sequence Carrier Proteins/physiology DNA-Binding Proteins/physiology Gene Expression Regulation/drug effects Genes, Homeobox Mice Molecular Sequence Data Oligodeoxyribonucleotides/chemistry Promoter Regions, Genetic Receptors, Retinoic Acid Regulatory Sequences, Nucleic Acid Transcription Factors/metabolism Tretinoin/pharmacology
Chemicals
Carrier Proteins DNA-Binding Proteins Oligodeoxyribonucleotides Receptors, Retinoic Acid Transcription Factors Tretinoin
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Pöpperl H
McGill Cancer Centre, Montréal, Québec, Canada.
Featherstone M S
References (67)
67 references, click to expand
  1. A versatile in vivo and in vitro eukaryotic expression vector for protein engineering.
    Nucleic Acids Res. 1988 Jan 11;16(1):369 PMID: 3340539
  2. Post-transcriptional regulation of a murine homeobox gene transcript in F9 embryonal carcinoma cells.
    Differentiation. 1987;35(3):206-11 PMID: 2895720
  3. Early retinoic acid-induced F9 teratocarcinoma stem cell gene ERA-1: alternate splicing creates transcripts for a homeobox-containing protein and one lacking the homeobox.
    Mol Cell Biol. 1988 Sep;8(9):3906-17 PMID: 2906112
  4. Hox-5.1 defines a homeobox-containing gene locus on mouse chromosome 2.
    Proc Natl Acad Sci U S A. 1988 Jul;85(13):4760-4 PMID: 2898782
  5. Differential expression of the homeobox gene Hox-1.3 in F9 embryonal carcinoma cells.
    Proc Natl Acad Sci U S A. 1988 Aug;85(15):5587-91 PMID: 2456573
  6. Vitamin D--soltriol the heliogenic steroid hormone: somatotrophic activator and modulator. Discoveries from histochemical studies lead to new concepts.
    Histochemistry. 1988;89(3):209-19 PMID: 3042715
  7. The estrogen receptor binds tightly to its responsive element as a ligand-induced homodimer.
    Cell. 1988 Oct 7;55(1):145-56 PMID: 3167974
  8. Purified hepatocyte nuclear factor 1 interacts with a family of hepatocyte-specific promoters.
    Proc Natl Acad Sci U S A. 1988 Nov;85(21):7937-41 PMID: 2460858
  9. Sequence elements in the human osteocalcin gene confer basal activation and inducible response to hormonal vitamin D3.
    Proc Natl Acad Sci U S A. 1989 Jun;86(12):4455-9 PMID: 2786632
  10. Cloning of murine alpha and beta retinoic acid receptors and a novel receptor gamma predominantly expressed in skin.
    Nature. 1989 Jun 29;339(6227):714-7 PMID: 2544807
  11. Differential expression of genes encoding alpha, beta and gamma retinoic acid receptors and CRABP in the developing limbs of the mouse.
    Nature. 1989 Dec 7;342(6250):702-5 PMID: 2556642
  12. Coordinate expression of the murine Hox-5 complex homoeobox-containing genes during limb pattern formation.
    Nature. 1989 Dec 14;342(6251):767-72 PMID: 2574828
  13. Mouse homeo-genes within a subfamily, Hox-1.4, -2.6 and -5.1, display similar anteroposterior domains of expression in the embryo, but show stage- and tissue-dependent differences in their regulation.
    Development. 1989 Sep;107(1):131-41 PMID: 2576400
  14. Luciferase reporter gene vectors for analysis of promoters and enhancers.
    Biotechniques. 1988 May;6(5):454-8 PMID: 2908509
  15. The mouse Hox-1.4 gene: primary structure, evidence for promoter activity and expression during development.
    Development. 1989 Oct;107(2):343-59 PMID: 2576648
  16. Polarizing activity and retinoid synthesis in the floor plate of the neural tube.
    Nature. 1990 Jun 28;345(6278):819-22 PMID: 2359459
  17. Sequential activation of HOX2 homeobox genes by retinoic acid in human embryonal carcinoma cells.
    Nature. 1990 Aug 23;346(6286):763-6 PMID: 1975088
  18. Molecular mechanisms underlying the expression of the human HOX-5.1 gene.
    Nucleic Acids Res. 1990 Aug 11;18(15):4361-8 PMID: 1975093
  19. Multiple cell type-specific proteins differentially regulate target sequence recognition by the alpha retinoic acid receptor.
    Cell. 1990 Nov 16;63(4):729-38 PMID: 2171781
  20. Interactions among a subfamily of nuclear hormone receptors: the regulatory zipper model.
    Mol Endocrinol. 1990 Sep;4(9):1293-301 PMID: 2172797
  21. A dominant negative mutation of the alpha retinoic acid receptor gene in a retinoic acid-nonresponsive embryonal carcinoma cell.
    Mol Cell Biol. 1990 Dec;10(12):6445-53 PMID: 2174108
  22. Identification of a DNA sequence responsible for binding of the 1,25-dihydroxyvitamin D3 receptor and 1,25-dihydroxyvitamin D3 enhancement of mouse secreted phosphoprotein 1 (SPP-1 or osteopontin) gene expression.
    Proc Natl Acad Sci U S A. 1990 Dec;87(24):9995-9 PMID: 2175918
  23. Regionally restricted developmental defects resulting from targeted disruption of the mouse homeobox gene hox-1.5.
    Nature. 1991 Apr 11;350(6318):473-9 PMID: 1673020
  24. Temporal and regional differences in the expression pattern of distinct retinoic acid receptor-beta transcripts in the chick embryo.
    Development. 1991 Jan;111(1):245-52 PMID: 1849811
  25. Retinoic acid receptors and cellular retinoid binding proteins. II. Their differential pattern of transcription during early morphogenesis in mouse embryos.
    Development. 1991 Jan;111(1):45-60 PMID: 1849812
  26. The late retinoic acid induction of laminin B1 gene transcription involves RAR binding to the responsive element.
    EMBO J. 1991 May;10(5):1149-58 PMID: 1850696
  27. LFB3, a heterodimer-forming homeoprotein of the LFB1 family, is expressed in specialized epithelia.
    EMBO J. 1991 Jun;10(6):1435-43 PMID: 1673925
  28. Sequence analysis of the homeobox-containing exon of the murine Hox-4.3 homeogene.
    Biochim Biophys Acta. 1991 Jun 13;1089(2):259-61 PMID: 1675873
  29. Direct repeats as selective response elements for the thyroid hormone, retinoic acid, and vitamin D3 receptors.
    Cell. 1991 Jun 28;65(7):1255-66 PMID: 1648450
  30. Independent regulation of HNF-1 alpha and HNF-1 beta by retinoic acid in F9 teratocarcinoma cells.
    EMBO J. 1991 Aug;10(8):2231-6 PMID: 2065662
  31. Retinoic acid receptors and cellular retinoid binding proteins. I. A systematic study of their differential pattern of transcription during mouse organogenesis.
    Development. 1990 Dec;110(4):1133-51 PMID: 1966045
  32. Retinoids, homeoboxes, and growth factors: toward molecular models for limb development.
    Cell. 1991 Jul 26;66(2):199-217 PMID: 1677315
  33. Differential regulation by retinoic acid of the homeobox genes of the four HOX loci in human embryonal carcinoma cells.
    Mech Dev. 1991 Mar;33(3):215-27 PMID: 1677812
  34. Disruption of the Hox-1.6 homeobox gene results in defects in a region corresponding to its rostral domain of expression.
    Cell. 1991 Sep 20;66(6):1105-19 PMID: 1680563
  35. Homeotic transformations of murine vertebrae and concomitant alteration of Hox codes induced by retinoic acid.
    Cell. 1991 Oct 4;67(1):89-104 PMID: 1680565
  36. Effects of retinoic acid excess on expression of Hox-2.9 and Krox-20 and on morphological segmentation in the hindbrain of mouse embryos.
    EMBO J. 1991 Oct;10(10):2985-95 PMID: 1915273
  37. A distinct Hox code for the branchial region of the vertebrate head.
    Nature. 1991 Oct 31;353(6347):861-4 PMID: 1682814
  38. The expression of murine Hox-2 genes is dependent on the differentiation pathway and displays a collinear sensitivity to retinoic acid in F9 cells and Xenopus embryos.
    Nucleic Acids Res. 1991 Oct 25;19(20):5497-506 PMID: 1682879
  39. Mouse retinoic acid receptor alpha 2 isoform is transcribed from a promoter that contains a retinoic acid response element.
    Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10138-42 PMID: 1658797
  40. Regulation of gene expression by retinoic acid receptors.
    DNA Cell Biol. 1991 Nov;10(9):623-38 PMID: 1661598
  41. HOX4 genes encode transcription factors with potential auto- and cross-regulatory capacities.
    EMBO J. 1991 Dec;10(13):4177-87 PMID: 1756725
  42. RXR beta: a coregulator that enhances binding of retinoic acid, thyroid hormone, and vitamin D receptors to their cognate response elements.
    Cell. 1991 Dec 20;67(6):1251-66 PMID: 1662118
  43. Homeobox genes and axial patterning.
    Cell. 1992 Jan 24;68(2):283-302 PMID: 1346368
  44. Purification, cloning, and RXR identity of the HeLa cell factor with which RAR or TR heterodimerizes to bind target sequences efficiently.
    Cell. 1992 Jan 24;68(2):377-95 PMID: 1310259
  45. Retinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors.
    Nature. 1992 Jan 30;355(6359):441-6 PMID: 1310350
  46. The upstream region of the human homeobox gene HOX3D is a target for regulation by retinoic acid and HOX homeoproteins.
    EMBO J. 1992 Jan;11(1):265-77 PMID: 1346761
  47. Developmental defects of the ear, cranial nerves and hindbrain resulting from targeted disruption of the mouse homeobox gene Hox-1.6.
    Nature. 1992 Feb 6;355(6360):516-20 PMID: 1346922
  48. Characterization of three RXR genes that mediate the action of 9-cis retinoic acid.
    Genes Dev. 1992 Mar;6(3):329-44 PMID: 1312497
  49. Cell adhesion molecules as targets for Hox genes: neural cell adhesion molecule promoter activity is modulated by cotransfection with Hox-2.5 and -2.4.
    Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2086-90 PMID: 1347944
  50. H-2RIIBP (RXR beta) heterodimerization provides a mechanism for combinatorial diversity in the regulation of retinoic acid and thyroid hormone responsive genes.
    EMBO J. 1992 Apr;11(4):1419-35 PMID: 1314168
  51. Homeosis in the mouse induced by a null mutation in the Hox-3.1 gene.
    Cell. 1992 Apr 17;69(2):251-64 PMID: 1348969
  52. Repression of the beta-amyloid gene in a Hox-3.1-producing cell line.
    Proc Natl Acad Sci U S A. 1992 May 1;89(9):3805-9 PMID: 1349171
  53. Retinoic acid causes abnormal development and segmental patterning of the anterior hindbrain in Xenopus embryos.
    Development. 1991 Dec;113(4):1145-58 PMID: 1811933
  54. Retinoic acid modifies development of the midbrain-hindbrain border and affects cranial ganglion formation in zebrafish embryos.
    Development. 1991 Dec;113(4):1159-70 PMID: 1811934
  55. Early events in mammalian craniofacial morphogenesis.
    J Craniofac Genet Dev Biol. 1991 Oct-Dec;11(4):181-91 PMID: 1812124
  56. Teratogenic effects of alcohol and isotretinoin on craniofacial development: an analysis of animal models.
    J Craniofac Genet Dev Biol. 1991 Oct-Dec;11(4):296-302 PMID: 1812131
  57. An autoregulatory element of the murine Hox-4.2 gene.
    EMBO J. 1992 Oct;11(10):3673-80 PMID: 1356763
  58. Identification of a retinoic acid responsive enhancer 3' of the murine homeobox gene Hox-1.6.
    Mech Dev. 1992 Sep;38(3):217-27 PMID: 1360810
  59. Retinoid-binding proteins in craniofacial development.
    J Craniofac Genet Dev Biol. 1991 Oct-Dec;11(4):303-14 PMID: 1667403
  60. Analysis of the murine Hox-2.7 gene: conserved alternative transcripts with differential distributions in the nervous system and the potential for shared regulatory regions.
    EMBO J. 1992 May;11(5):1825-36 PMID: 1582411
  61. Targeted misexpression of Hox-4.6 in the avian limb bud causes apparent homeotic transformations.
    Nature. 1992 Jul 16;358(6383):236-9 PMID: 1352858
  62. A human HOX4B regulatory element provides head-specific expression in Drosophila embryos.
    Nature. 1992 Jul 23;358(6384):345-7 PMID: 1353609
  63. A new technique for the assay of infectivity of human adenovirus 5 DNA.
    Virology. 1973 Apr;52(2):456-67 PMID: 4705382
  64. Retinoic acid embryopathy.
    N Engl J Med. 1985 Oct 3;313(14):837-41 PMID: 3162101
  65. Abundant expression of homeobox genes in mouse embryonal carcinoma cells correlates with chemically induced differentiation.
    Proc Natl Acad Sci U S A. 1987 Mar;84(5):1304-8 PMID: 2434952
  66. Region-specific enhancers near two mammalian homeo box genes define adjacent rostrocaudal domains in the central nervous system.
    Genes Dev. 1990 Feb;4(2):180-9 PMID: 1970971
  67. Rapid and efficient site-specific mutagenesis without phenotypic selection.
    Methods Enzymol. 1987;154:367-82 PMID: 3323813
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.13.1.257-265.1993
Published
1993-01-00
Pages
257-65
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC358905
Subset
IM
Databases
GENBANK
X65950
External Links
PubMed source DOI: 10.1128/mcb.13.1.257-265.1993 PMC Full Text View journal details
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