CIONA-INTESTINALIS NUCLEAR RECEPTOR-1 - A MEMBER OF STEROID THYROID HORMONE-RECEPTOR FAMILY/

Nuclear hormone receptors comprise a large family of zinc finger trans cription factors, some with hydrophobic Ligands, such as thyroid hormo ne, vitamin D, steroids, etc., and others for which no ligand has been found. Thyroid hormone receptors (TRs) generally are considered to be confined to the vertebrata that possess a thyroid gland, Tunicates re present the most primitive of the chordates, and there are data suppor ting a role for thyroid hormone in their metamorphosis, but no data ar e available on TRs in this genus; hence, we have studied Ciona intesti nalis. Screening of a Ciona library with the DNA binding domain of Xen opus laevis TR (xTR) resulted in the isolation of a nuclear hormone re ceptor, C. intestinalis nuclear receptor 1 (CiNR1), CiNR1 is similar t o TRs of more evolved species with a conserved DNA binding domain wher eas the ligand binding domain shows poor homology to vertebrate sequen ces. The C-terminal part of CiNR1 spans approximate to 200 amino acids more than other TRs, lacks the AF2 transactivation domain, and is not able to bind triiodothyronine, Phylogenetically, CiNR1 appears to be close to the common ancestral gene of TRs. Expression of CiNR1 was lim ited to the developing embryo and the larval stage, which suggests a r ole during development and metamorphosis, In transfection experiments, CiNR1 down-regulated basal transcription of a reporter gene driven by the TR palindrome responsive element. When CiNR1 was cotransfected wi th chicken TR alpha, it attenuated the normal thyroid hormone response in a dominant negative fashion. This attenuation required the C-termi nal portion of the molecule.