Identification of a Retinoic Acid Response Element Upstream of the Murine Hox-4.2 Gene

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 1993 Jan 1

PMID 8093325

Citations 26

Authors

H Popperl

M S Featherstone

Affiliations

Soon will be listed here.

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.

Citing Articles

The E3 ubiquitin ligase RNF220 maintains hindbrain expression patterns through regulation of WDR5 stability.

Wang H, Liu X, Liu Y, Yang C, Ye Y, Yu X Elife. 2024; 13.

PMID: 39526890 PMC: 11554307. DOI: 10.7554/eLife.94657.

Retinoic Acid Regulates Spermiogenesis Via Hoxb1 and Shh Signaling in Testicular Germ Cells.

Pallavi S, Jain S, Mohanty S, Andrabi S, Rajender S Reprod Sci. 2024; 31(11):3400-3412.

PMID: 39080234 DOI: 10.1007/s43032-024-01648-y.

Hindbrain induction and patterning during early vertebrate development.

Frank D, Sela-Donenfeld D Cell Mol Life Sci. 2018; 76(5):941-960.

PMID: 30519881 PMC: 11105337. DOI: 10.1007/s00018-018-2974-x.

HOX genes: Major actors in resistance to selective endocrine response modifiers.

Jin K, Sukumar S Biochim Biophys Acta. 2016; 1865(2):105-10.

PMID: 26803986 PMC: 4860125. DOI: 10.1016/j.bbcan.2016.01.003.

Thymosin-β4 is a determinant of drug sensitivity for Fenretinide and Vorinostat combination therapy in neuroblastoma.

Cheung B, Tan O, Koach J, Liu B, Shum M, Carter D Mol Oncol. 2015; 9(7):1484-500.

PMID: 25963741 PMC: 5528804. DOI: 10.1016/j.molonc.2015.04.005.

References

Green S, Issemann I, Sheer E . A versatile in vivo and in vitro eukaryotic expression vector for protein engineering. Nucleic Acids Res. 1988; 16(1):369. PMC: 334650. DOI: 10.1093/nar/16.1.369. View

Colberg-Poley A, Puschel A, Dony C, Voss S, Gruss P . Post-transcriptional regulation of a murine homeobox gene transcript in F9 embryonal carcinoma cells. Differentiation. 1987; 35(3):206-11. DOI: 10.1111/j.1432-0436.1987.tb00170.x. View

LaRosa G, Gudas L . 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; 8(9):3906-17. PMC: 365450. DOI: 10.1128/mcb.8.9.3906-3917.1988. View

Featherstone M, Baron A, Gaunt S, Mattei M, Duboule D . Hox-5.1 defines a homeobox-containing gene locus on mouse chromosome 2. Proc Natl Acad Sci U S A. 1988; 85(13):4760-4. PMC: 280515. DOI: 10.1073/pnas.85.13.4760. View

Murphy S, Garbern J, Odenwald W, Lazzarini R, Linney E . Differential expression of the homeobox gene Hox-1.3 in F9 embryonal carcinoma cells. Proc Natl Acad Sci U S A. 1988; 85(15):5587-91. PMC: 281804. DOI: 10.1073/pnas.85.15.5587. View

Stumpf W . 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. DOI: 10.1007/BF00493142. View

Kumar V, Chambon P . The estrogen receptor binds tightly to its responsive element as a ligand-induced homodimer. Cell. 1988; 55(1):145-56. DOI: 10.1016/0092-8674(88)90017-7. View

Courtois G, Baumhueter S, Crabtree G . Purified hepatocyte nuclear factor 1 interacts with a family of hepatocyte-specific promoters. Proc Natl Acad Sci U S A. 1988; 85(21):7937-41. PMC: 282328. DOI: 10.1073/pnas.85.21.7937. View

Kerner S, Scott R, Pike J . 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; 86(12):4455-9. PMC: 287288. DOI: 10.1073/pnas.86.12.4455. View

10.

Zelent A, Krust A, Petkovich M, Kastner P, Chambon P . Cloning of murine alpha and beta retinoic acid receptors and a novel receptor gamma predominantly expressed in skin. Nature. 1989; 339(6227):714-7. DOI: 10.1038/339714a0. View

11.

Dolle P, Ruberte E, Kastner P, Petkovich M, Stoner C, Gudas L . Differential expression of genes encoding alpha, beta and gamma retinoic acid receptors and CRABP in the developing limbs of the mouse. Nature. 1989; 342(6250):702-5. DOI: 10.1038/342702a0. View

12.

Dolle P, Izpisua-Belmonte J, Falkenstein H, Renucci A, Duboule D . Coordinate expression of the murine Hox-5 complex homoeobox-containing genes during limb pattern formation. Nature. 1989; 342(6251):767-72. DOI: 10.1038/342767a0. View

13.

Gaunt S, Krumlauf R, Duboule D . 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; 107(1):131-41. DOI: 10.1242/dev.107.1.131. View

14.

Nordeen S . Luciferase reporter gene vectors for analysis of promoters and enhancers. Biotechniques. 1988; 6(5):454-8. View

15.

Galliot B, Dolle P, Vigneron M, Featherstone M, Baron A, Duboule D . The mouse Hox-1.4 gene: primary structure, evidence for promoter activity and expression during development. Development. 1989; 107(2):343-59. DOI: 10.1242/dev.107.2.343. View

16.

Wagner M, Thaller C, Jessell T, Eichele G . Polarizing activity and retinoid synthesis in the floor plate of the neural tube. Nature. 1990; 345(6278):819-22. DOI: 10.1038/345819a0. View

17.

Simeone A, Acampora D, Arcioni L, Andrews P, Boncinelli E, Mavilio F . Sequential activation of HOX2 homeobox genes by retinoic acid in human embryonal carcinoma cells. Nature. 1990; 346(6286):763-6. DOI: 10.1038/346763a0. View

18.

Cianetti L, Di Cristofaro A, Zappavigna V, Bottero L, Boccoli G, Testa U . Molecular mechanisms underlying the expression of the human HOX-5.1 gene. Nucleic Acids Res. 1990; 18(15):4361-8. PMC: 331252. DOI: 10.1093/nar/18.15.4361. View

19.

Glass C, Devary O, Rosenfeld M . Multiple cell type-specific proteins differentially regulate target sequence recognition by the alpha retinoic acid receptor. Cell. 1990; 63(4):729-38. DOI: 10.1016/0092-8674(90)90139-6. View

20.

Forman B, Samuels H . Interactions among a subfamily of nuclear hormone receptors: the regulatory zipper model. Mol Endocrinol. 1990; 4(9):1293-301. DOI: 10.1210/mend-4-9-1293. View