Maeng, Sejung Lee, Jung Hwan Kim, Gil Jung Kim, Sung Hun Kwon, Hak Cheol Shin, Yun Kyung Sohn, Young Chang 2024-01-20T15:06:16Z 2024-01-20T15:06:16Z 2021-09-04 2012-03 1096-4959 https://pubs.kist.re.kr/handle/201004/129504 The farnesoid X receptors (FXRs) are the major transcriptional regulators of bile salt synthesis in vertebrates. However, the structural conservation of invertebrate FXRs has only been studied for the major model organisms and studies on additional invertebrate FXRs are clearly required to obtain better resolution of FXR phylogeny and comparative developmental insights in chordates. In the present study, the cDNA encoding the farnesoid X receptor, HrFXR, was cloned from a marine invertebrate Halocynthia roretzi. The open reading frame of HrFXR encoded 688 amino acids including a longer N-terminal region and showed overall sequence identities of 28-41% to vertebrate and Ciona intestinalis FXRs. The N-terminal activation function 1 (AF-1) and hinge domains of HrFXR displayed relatively low identities (<20%), whereas the DNA-binding and ligand-binding domains showed relatively high (>73%) and intermediate (21-50%) identities, respectively. Based on a phylogenetic analysis, HrFXR belonged to a urochordate group, which was placed differently from vertebrate FXR alpha and FXR beta subgroups. Real-time quantitative PCR analysis revealed that the HrFXR mRNA originated maternally and was highly expressed in adult gonads. Additionally, HrFXR mRNA levels in the gills and hepatopancreas showed significantly higher values in animals with soft tunic syndrome compared to those of normal individuals. Furthermore, direct injection of cholic acid significantly increased HrFXR transcript levels in vivo, although an expression vector containing HrFXR cDNA did not show a significant transactivation function in response to a well-known ligand for vertebrate FXR, GW4064, in HepG2 cells. These results suggest that the tunicate FXR has different structural and expressional characteristics compared to those of vertebrate FXRs. (C) 2011 Elsevier Inc. All rights reserved. English ELSEVIER SCIENCE INC NUCLEAR HORMONE-RECEPTORS SOFT TUNIC SYNDROME BILE-ACIDS GENE-EXPRESSION EVOLUTION GENOME FXR IDENTIFICATION SUPERFAMILY VERTEBRATES Molecular and expression analysis of the farnesoid X receptor in the urochordate Halocynthia roretzi Article 10.1016/j.cbpb.2011.11.004 1 COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY, v.161, no.3, pp.189 - 196 COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY 161 3 189 196 scie scopus 000300808500001 2-s2.0-84856221129 Biochemistry & Molecular Biology Zoology Biochemistry & Molecular Biology Zoology Article NUCLEAR HORMONE-RECEPTORS SOFT TUNIC SYNDROME BILE-ACIDS GENE-EXPRESSION EVOLUTION GENOME FXR IDENTIFICATION SUPERFAMILY VERTEBRATES FXR Embryo Invertebrate Ascidian Soft tunic syndrome