GENES ANCESTRAL TO THE THYROID/STEROID RECEPTOR FAMILY

我们小组一直在调查甲状腺/类固醇激素的成员

Our group has been investigating members of thyroid/steroid hormone receptor family in lower organisms in an attempt to analyze the structure and functions of the most primitive receptors, better to understand the function of the myriad of receptors present in the vertebrata. We cloned cDNAs for three such proteins in the nematode Caenorhabditis elegans. One of them (CHR3) is highly homologous to the DHR3 in Drosophila and MHR3 in Manduca sexta. This receptor in Drosophila is induced by ecdysone. Another receptor we cloned (CNR14) is homologous to E78A receptor, also ecdysone inducible in Drosophila. The third receptor, CNR8 is similar to an early response gene in vertebrates, NAK1. The receptors are stage specific as shown by Northern analysis. More recently, we have cloned the genes for CHR3 and CNR14 and we are studying their promoters. We found that two genes, CHR3 and CNR14 are trans-spliced and so are organized in operons. While CHR3 is trans-spliced with a leader sequence SL2, and CNR14 is trans-spliced with SL1, CNR8 seems to be transcribed as single transcript. Cistronic transcription gives us the opportunity to study the genes which are transcribed from a common promoter and which could function together. We mapped CHR3 to the center region of chromosome 1 in close relation to hlh-2 gene, a homeobox protein analogous to E12 protein, the partner of MyoD in vertebrates. We confirmed the propinquity of the hlh-2 and CHR3 by PCR on a cosmid. Interestingly, some known mutants with deletion in this region are lethal. We are currently studying expression of CHR3 and CNR14 using microinjetions to the ovary of hermaphrodites with probable promoter regions coupled to DNA sequence coding for beta-galactosidase. We also hope to use heterozygotic strains with deletions in a region where CHR3 maps for a study of knock-out and rescue. We continued on the steroid hormone receptor in cubomedusan jellyfish Tripedalia cystophora. We cloned at least two cDNA isoforms and most of the gene. As far as we can tell, this is the only such gene in his organism and could represent the most primitive member of thyroid/retinoic acid subfamily.