Steroid/thyroid hormone receptor genes in Caenorhabditis elegans.

Abstract

The large family of steroid/thyroid hormone receptor (STR) genes has been extensively studied in vertebrates and insects but little information is available on it in more primitive organisms. All members possess a DNA binding domain of zinc fingers of the C2, C2 type. We have used the polymerase chain reaction with degenerate oligonucleotide primers covering this region to clone three distinct members of this family from the nematode Caenorhabditis elegans. All three belong to the retinoic acid receptor (RAR), thyroid hormone receptor subfamily of genes. The cDNA of one of these clones shows such a high homology to DHR3, an early ecdysone response gene found in Drosophila, and MHR3, identified in Manduca sexta, that we have termed it CHR3. Furthermore, the C-terminal portion of the deduced protein sequence shows a box containing eight identical amino acids among CHR3, DHR3, and MHR3 suggesting an identical specific ligand for these proteins. CNR8 shows homology to NAK1, and CNR14 has homology to both the RAR-yl gene and to another ecdysone response gene, E78A. Neither of the latter two cDNAs is a clear homologue of any known gene and each is distinctive. All of these genes are expressed varyingly in both larval and adult stages of nematode development as shown by Northern blot analyses. These data demonstrate that the STR family of genes is represented in a nematode whose ancestor appeared well before the branching that gave rise to the Arthropoda and Chordata.More than 200 different cDNAs of the steroid/thyroid hormone receptor (STR) gene family have been cloned and sequenced from a variety of organisms. Many of these sequences are clear homologues-i.e., the thyroid hormone receptor (TR) genes from rat, chicken, mouse, human, and frog code for a highly similar protein that binds thyroid hormone. However, the term homologue can be ambiguous; in addition to the above, it can also mean evolutionarily related, as are all of these STR genes whether they bind steroids, retinoids, or thyroid hormone or have no known ligands. Our interest has been to discern the evolutionary history of this gene family. The family has been variously divided into 3-10 different groups (1-3). Sequences are available mostly from vertebrates and arthropods, although one sequence is known from an echinoderm (4). All of these genes can be divided into five or six domains denoted A-F (2, 3) (see Fig. 4 A). The A/B domain is most N terminal and is poorly conserved. The C domain is the zinc finger DNA binding domain and is so highly conserved as to identify the superfamily (5). The sequence of the distal part of the first zinc finger, termed the P box, distinguishes the three main subfamilies of the STR (2). The D, E, and F domains contain the activating domain, a dimerization domain, and the ligand binding domain (2, 3, 6, 7). We have searched for related genes in several invertebrate phyla and report here the identification and cDNA sequences of three genes from Caenorhabditis elegans. t The sequences of the P box of the cDNAs we have...

Nuclear hormone receptor CHR3 is a critical regulator of all four larval molts of the nematodeCaenorhabditis elegans

“…As reported earlier, CHR3 is present in epidermal cells throughout development based on gfp reporter genes, antibody staining (embryos only), and Northern analysis (16,19). To measure the level of CHR3 (nhr-23) expression during molting cycles, we used synchronized populations of larvae and evaluated the expression of CHR3 (nhr-23) by RT-PCR.…”

“…We have retested the effects of nhr-25 RNAi applied to young larvae by using the feeding technique. Although we can induce by feeding many of the phenotypic defects reported previously by microinjection (18,19), only about 1% of the animals showed signs of impaired molting. The low penetrance of molting defects and lack of effect of CHR3 (nhr-23) RNAi on nhr-25::gfp expression suggest that nhr-25 is not acting downstream of CHR3 (nhr-23) in the C. elegans molting pathway.…”

“…We previously have cloned the C. elegans orphan NHR CHR3 (19), which is a homologue of Drosophila DHR3 (20), Manduca sexta MHR3 (21), and mammalian ROR͞RZR͞Rev ErbA (22,23). For clarity, we refer to it in this paper by using both its common and gene names, CHR3 (nhr-23).…”

Retinoid-Related Orphan Receptor α Controls the Early Steps of Purkinje Cell Dendritic Differentiation

“…In insects, dendritic remodeling seems to be regulated by the steroid hormone 20-hydroxyecdysone (referred as ecdysone) in Manduca sexta or in Drosophila melanogaster (Weeks, 2003). Interestingly, ecdysone induces expression of the Caenorhabditis elegans CHR3 (Kostrouch et al, 1995), Drosophila DHR3 (Koelle et al, 1992), and Manduca sexta MHR3 (Palli et al, 1992) genes, which are homologs of the mammalian Rora gene. ROR␣ plays a role in the regressive and remodeling events of the normal dendritic differentiation of PCs, events that are comparable with those induced by the ecdysone pathway in insects.…”

Evolution of the nuclear receptor superfamily: early diversification from an ancestral orphan receptor

“…This suggests that the appearance of the first receptor was extremely early. Interestingly, some members of the family have been cloned from the nematode Caenorhabditis elegans (Sengupta et al 1994, Kostrouch et al 1995. A divergent member of subfamily I was also described in Onchocerca volvulus (Goffeau et al 1996).…”