Retinoic acid X receptor in the diploblast, Tripedalia cystophora.

Nuclear hormone receptors comprise a characteristic family of transcription factors found in vertebrates, insects and nematodes. Here we show by cDNA and gene cloning that a Cnidarian, Tripedalia cystophora, possesses a retinoid receptor (jRXR) with remarkable homology to vertebrate retinoic acid X receptors (RXRs). Like vertebrate RXRs, jRXR binds 9-cis retinoic acid (Kd = 4 x 10(-10) M) and binds to the DNA sequence, PuGGTCA as a monomer in vitro. jRXR also heterodimerizes with Xenopus TR beta on a thyroid responsive element of a direct repeat separated by 4 bp. A jRXR binding half-site capable of interacting with (His6)jRXR fusion protein was identified in the promoters of three T. cystophora crystallin genes that are expressed highly in the eye lens of this jellyfish. Because crystallin gene expression is regulated by retionoid signaling in vertebrates, the jellyfish crystallin genes are candidate in vivo targets for jRXR. Finally, an antibody prepared against (His6)jRXR showed that full-length jRXR is expressed at all developmental stages of T. cystophora except the ephydra, where a smaller form replaces is. These data show that Cnidaria, a diploblastic phylum ancestral to the triploblastic invertebrate and subsequent vertebrate lineages, already have an RXR suggesting that RXR is an early component of the regulatory mechanisms of metazoa.

[1]  J. W. Valentine.  Cleavage patterns and the topology of the metazoan tree of life. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[2]  K. Umesono,et al.  The nuclear receptor superfamily: The second decade , 1995, Cell.

[3]  V. Giguère,et al.  Functional Interactions between Retinoic Acid Receptor-related Orphan Nuclear Receptor (RORα) and the Retinoic Acid Receptors in the Regulation of the γF-Crystallin Promoter (*) , 1995, The Journal of Biological Chemistry.

[4]  D. Mangelsdorf,et al.  Activation of the orphan nuclear receptor steroidogenic factor 1 by oxysterols. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Jasmine Chen,et al.  Identification of a nuclear receptor that is activated by farnesol metabolites , 1995, Cell.

[6]  C. Hänni,et al.  Ligand binding was acquired during evolution of nuclear receptors. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[7]  J. Vonesch,et al.  Genetic analysis of RXRα developmental function: Convergence of RXR and RAR signaling pathways in heart and eye morphogenesis , 1994, Cell.

[8]  H. Sambrook.  Molecular cloning : a laboratory manual. Cold Spring Harbor, NY , 1989 .

[9]  BERNHARD WERNER,et al.  Life Cycle of Tripedalia cystophora Conant (Cubomedusae) , 1971, Nature.

[10]  R. Evans,et al.  The RXR heterodimers and orphan receptors , 1995, Cell.

[11]  J. E. Rall,et al.  Steroid/thyroid hormone receptor genes in Caenorhabditis elegans. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[12]  K. Umesono,et al.  BXR, an embryonic orphan nuclear receptor activated by a novel class of endogenous benzoate metabolites. , 1998, Genes & development.

[13]  V. Laudet,et al.  Evolution of the nuclear receptor superfamily: early diversification from an ancestral orphan receptor. , 1997, Journal of molecular endocrinology.

[14]  J. Piatigorsky,et al.  J1-crystallins of the cubomedusan jellyfish lens constitute a novel family encoded in at least three intronless genes. , 1993, The Journal of biological chemistry.

[15]  M. Mckeown,et al.  Relationship between the product of the Drosophila ultraspiracle locus and the vertebrate retinoid X receptor , 1990, Nature.

[16]  L. Tsui,et al.  Heterodimeric interaction of the retinoic acid and thyroid hormone receptors in transcriptional regulation on the gamma F-crystallin everted retinoic acid response element. , 1994, Molecular endocrinology.

[17]  D. Martinez,et al.  Cnidarian homeoboxes and the zootype , 1998, Nature.

[18]  A. Cvekl,et al.  Involvement of Retinoic Acid/Retinoid Receptors in the Regulation of Murine αB-crystallin/Small Heat Shock Protein Gene Expression in the Lens* , 1998, The Journal of Biological Chemistry.

[19]  A. Cvekl,et al.  Lens‐preferred activity of chicken δ1‐ and δ2‐crystallin enhancers in transgenic mice and evidence for retinoic acid‐responsive regulation of the δ1‐crystallin gene , 1997 .

[20]  P. Sharp,et al.  Ultraspiracle: an invertebrate nuclear receptor for juvenile hormones. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[21]  M. Johnston,et al.  Identification of the DNA binding site for NGFI-B by genetic selection in yeast. , 1991, Science.

[22]  R. Clayton,et al.  Age-related changes in the response of chick lens cells during long-term culture to insulin, cyclic AMP, retinoic acid and a bovine retinal extract. , 1990, Experimental eye research.

[23]  L. Tsui,et al.  An everted repeat mediates retinoic acid induction of the gamma F-crystallin gene: evidence of a direct role for retinoids in lens development. , 1993, Genes & development.

[24]  K. Umesono,et al.  Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling , 1992, Nature.

[25]  J. Repa,et al.  Generating and characterizing retinoid receptors from Escherichia coli and insect cell expression systems. , 1997, Methods in enzymology.

[26]  V. Laudet,et al.  Evolution of the nuclear receptor gene superfamily. , 1992, The EMBO journal.

[27]  Jasmine Chen,et al.  The orphan nuclear receptor LXRalpha is positively and negatively regulated by distinct products of mevalonate metabolism. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[28]  D. Hewett‐Emmett,et al.  Evolution of paired domains: isolation and sequencing of jellyfish and hydra Pax genes related to Pax-5 and Pax-6. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[29]  J. Grippo,et al.  9-Cis retinoic acid stereoisomer binds and activates the nuclear receptor RXRα , 1992, Nature.

[30]  A. Cvekl,et al.  Lens development and crystallin gene expression: many roles for Pax‐6 , 1996, BioEssays : news and reviews in molecular, cellular and developmental biology.

[31]  E. Linney,et al.  The mouse retinoid-X receptor-gamma gene: genomic organization and evidence for functional isoforms. , 1993, Molecular endocrinology.

[32]  Y. Kanno,et al.  The mouse Rxrb gene encoding RXR beta: genomic organization and two mRNA isoforms generated by alternative splicing of transcripts initiated from CpG island promoters. , 1994, Gene.