FTZ-F1-related orphan receptors in Xenopus laevis: transcriptional regulators differentially expressed during early embryogenesis.

Abstract

Orphan receptors of the FTZ-F1-related group of nuclear receptors (xFFlr) were identified in Xenopus laevis by isolation of cDNAs from a neurula stage library. Two cDNAs were found, which encode full-length, highly related receptor proteins, xFFlrA and B, whose closest relative known so far is the murine LRH-1 orphan receptor. xFFIrA protein expressed by a recombinant vaccinia virus system specifically binds to f1Z-F1 response elements (FRE; PyCAAGGPyCPu). In cotransfection studies, xFF1rA constitutively activates transcription, in a manner dependent on the number of FREs. The amounts of at least four mRNAs encoding full-length receptors greatly increase between gastrula and early tailbud stages and decrease at later stages. At early tailbud stages, xFTZ-F1-related antigens are found in all nuclei of the embryo.The nuclear hormone receptor superfamily includes receptors for steroid and thyroid hormones, vitamin D and retinoic acid, which regulate gene expression in the presence of their respective ligands by binding to cis-acting DNA sequences called hormone response elements (HRE) (53). These nuclear receptors, which control different developmental and physiological processes, share several structural and functional features. They are composed of six domains, A to F, of which the most highly conserved Zn-finger-containing C domain is responsible for specific DNA binding (25). In addition to ligand binding, the E domain appears to be involved in dimerization and transcriptional activation or repression (12,53).Recently, a number of receptors have been identified for which a ligand has not yet been found or may not exist. However, these orphan receptors are structurally related to other nuclear receptors and, thus, are included in the nuclear receptor superfamily (27,41). This superfamily can be divided into subfamilies on the basis of either characteristic amino acid sequence motifs of its members (53), their evolutionary relationships (27), or functional criteria, such as the ability to bind to distinct HREs (27,42,46

The Mouse Fetoprotein Transcription Factor (FTF) Gene Promoter Is Regulated by Three GATA Elements with Tandem E Box and Nkx Motifs, and FTF in Turn Activates the Hnf3β, Hnf4α, and Hnf1α Gene Promoters

“…The partial mFTF gene structure established here indicates an intron/exon organization similar to that of the Sf1 gene, which was duplicated from the same ancestral gene (14). Like in man, the mouse Sf1 and FTF genes reside on different chromosomes (16,29,30).…”

“…Early developmental patterns of FTF expression in several species (14,17,19) and its activation of the AFP locus in hepatocyte progenitors suggested an important role for FTF in endodermal differentiation pathways. To gain better insight into FTF functions and its position in liver induction pathways, we isolated and functionally characterized the mouse FTF gene promoter in search for upstream FTF gene regulators, and we also searched for new FTF downstream gene targets.…”

The Fetoprotein Transcription Factor (FTF) Gene Is Essential to Embryogenesis and Cholesterol Homeostasis and Is Regulated by a DR4 Element

“…FTF is also ubiquitously expressed in the early embryo, like its homolog in Xenopus (38), and FTF is essential to mouse embryogenesis, like its distant relative Ftz-F1 in Drosophila (39). In contrast, SF1, the closest FTF homolog, is specifically required for development of steroidogenic organs (40).…”

Molecular Cloning and Expression Analysis of FTZ-F1 in the Half-smooth Tongue-sole,<I>Cynoglossus semilaevis</I>

“…FTZ-F1 homologues have been identified in human, mouse, Xenopus laevis and in a number of teleost species (Oba et al, 1996;Lala et al, 1992;Ellinger-Ziegelbauer et al, 1994;Zhang et al, 2006, Chai & Chan, 2000Watanabe et al, 1999;Von et al, 2002). In mammals these genes have been classified as either SF-1/Ad4BP (steroidogenic factor-1/adrenal 4 binding protein) or LRH/FTF (liver receptor hormone/a-fetoprotein transcription factor) related.…”