Genomic structure of the Xenopus laevis liver transcription factor LFB1

Zapp, D; Bartkowski, S; Zoidl, Christiane; Klein-Hitpaß, Ludger; Ryffel, Gerhart U.

doi:10.1016/0378-1119(93)90102-9

Cited by 6 publications

(3 citation statements)

References 14 publications

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“…The 5a insertion into the Pax6 paired domain is the first example of an insertion into the turn region of a HTH motif that destabilizes its ability to interact with DNA. Like the 21-residue insertion in LFB 1 (Bach et al 1992;Zapp et al 1993), the 5a insertion occurs at an intron--exon boundary in genomic DNA, indicating that modification of the turn region may be an evolutionary strategy for modulating the DNA-binding properties of the HTH motif.…”

Section: The 5a Insertion Functions As a Molecular Togglementioning

confidence: 99%

Two independent and interactive DNA-binding subdomains of the Pax6 paired domain are regulated by alternative splicing.

Epstein¹,

Gläser²,

Cai³

et al. 1994

Genes Dev.

331

342

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Vertebrate Pax proteins share a conserved 128-amino-acid DNA-binding motif, the paired domain. The PAX6 gene, which is mutated in the routine Small eye and human aniridia developmental defects, also encodes a second protein with a 14-amino-acid insertion in the paired domain. This protein, which arises by alternative mRNA splicing, exhibits unique DNA-binding properties. Unlike other paired domains, which bind DNA predominantly by their amino termini, the extended Pax6 paired domain interacts with DNA exclusively through its carboxyl terminus. This property can be simulated by deletion of 30 amino-terminal residues from the Pax6 or Pax2 paired domains. Thus, the insertion acts as a molecular toggle to unmask the DNA-binding potential of the carboxyl terminus. The functional nonequivalence of the two Pax6 proteins is underscored by a T ~ C mutation at position -3 of the alternative splice acceptor site that changes the ratio of the two isoforms and causes a distinct human ocular syndrome.

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Section: The 5a Insertion Functions As a Molecular Togglementioning

confidence: 99%

Two independent and interactive DNA-binding subdomains of the Pax6 paired domain are regulated by alternative splicing.

Epstein¹,

Gläser²,

Cai³

et al. 1994

Genes Dev.

331

342

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“…Both transcription factors are encoded in distinct genes on separate chromosomes, and are highly conserved in vertebrates with homologues in fish [4,5], frog [6,7] and mammals, including humans [8][9][10]. The evolutionary conservation is also seen in the exon/intron patterning which remains essentially the same between Xenopus and mammals [11]. Both HNF1 proteins contain a highly conserved N-terminal dimerization domain, a bipartite DNA binding region and a more divergent C-terminal transactivation domain ( Fig.…”

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confidence: 99%

The HNF1β transcription factor has several domains involved in nephrogenesis and partially rescues Pax8/lim1‐induced kidney malformations

Bohn

Ryffel

2004

European Journal of Biochemistry

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The tissue-specific transcription factors HNF1alpha and HNF1beta are closely related homeodomain proteins conserved in vertebrate evolution. Heterozygous mutations in human HNF1beta but not in HNF1alpha genes are associated with kidney malformations. Overexpression of HNF1beta in Xenopus embryos leads to defective pronephros development, while HNF1alpha has no effect. We have defined the regions responsible for this functional difference between HNF1beta and HNF1alpha in transfected HeLa cells as well as in injected Xenopus embryos. Using domain swapping experiments, we located a nuclear localization signal in the POUH domain of HNF1beta, and showed that the POUS and POUH domains of HNF1beta mediate a high transactivation potential in transfected cells. In injected Xenopus embryos three HNF1beta domains are involved in nephrogenesis. These include the dimerization domain, the 26 amino acid segment specific for splice variant A as well as the POUH domain. As HNF1beta together with Pax8 and lim1 constitute the earliest regulators in the pronephric anlage, it is possible that they cooperate during early nephrogenesis. We have shown here that HNF1beta can overcome the enlargement and the induction of an ectopic pronephros mediated by overexpression of Pax8 and lim1. However, the phenotype induced by Pax8 and lim1 overexpression and characterized by cyst-like structures and thickening of the pronephric tubules was not altered by HNF1beta overexpression. Taken together, HNF1beta acts antagonistically to Pax8 and lim1 in only some processes during nephrogenesis, and a simple antagonistic relationship does not completely describe the functions of these genes. We conclude that HNF1beta has some distinct morphogenetic properties during nephrogenesis.

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“…Prior to injection, the embryos were dejellied in 2% cysteine-HCl (pH 8.0) and then washed in 25 mM NaCl. Embryos were injected in lx NAM (normal amphibian medium [40] (50).…”

Section: Methodsmentioning

confidence: 99%

Elements and factors involved in tissue-specific and embryonic expression of the liver transcription factor LFB1 in Xenopus laevis.

Zapp¹,

Bartkowski²,

Holewa³

et al. 1993

Mol. Cell. Biol.

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LFB1 (HNF1) is a tissue-specific transcription factor found in the livers, stomachs, intestines, and kidneys of vertebrates. By analyzing the promoter of the Xenopus LFB1 gene, we identified potential autoregulation by LFB1 and regulation by HNF4, a transcription factor with a tissue distribution similar to that of LFB1.Injection of LFB1 promoter-chloramphenicol acetyltransferase constructs into Xenopus eggs revealed embryonic activation that is restricted to the region of the developing larvae expressing endogeneous LFB1. Proper embryonic activation was also observed with a rat LFB1 promoter. Deletion analysis of the Xenopus and rat promoters revealed that in both promoters embryonic activation is absolutely dependent on the presence of an element that contains CCNCTCTC as the core consensus sequence. Since this element is recognized by the maternal factor OZ-1 previously described by N. Ovsenek, A. M. Zorn, and P. A. Krieg (Development 115:649-655, 1992), we might have identified the main constituents of a hierarchy that leads via LFB1 to the activation of tissue-specific genes during embryogenesis.Tissue-specific expression of genes is achieved to a large extent by the interaction of transcription factors with cisacting elements present in the promoters and enhancers of genes that are expressed differently in different tissues. These transcription factors themselves are tissue specific. This restricted expression pattern is established sometime during embryogenesis, and we assume that it plays a key role in the differentiation processes. Molecular analysis of early vertebrate development has established a complex hierarchy of regulatory factors involved in establishing the body plan (for recent reviews, see references 12 and 15). Some of the genes encoding these factors are the homeobox genes known to be conserved between Drosophila melanogaster and mammals (for a recent review, see reference 26). There is increasing evidence that these genes form a very complex regulatory network in which specific genes influence the activities of other genes. Typically these regulatory genes are expressed in distinct areas of the embryo and may be active only transiently during embryogenesis. There is, at least in the case of D. melanogaster, clear evidence that some transcription factors are already present in fertilized eggs, and it is assumed that these maternal factors are responsible for initiating gene activation in early embryogenesis (for a recent review, see reference 16). So far no direct link between the early active transcription factors and the expression of tissue-specific transcription factors could be made. In one approach to this question, we analyzed the regulatory elements and factors involved in embryonic activation of the promoter of the liver transcription factor LFB1 (HNF1) in Xenopus laevis.

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Genomic structure of the Xenopus laevis liver transcription factor LFB1

Cited by 6 publications

References 14 publications

Two independent and interactive DNA-binding subdomains of the Pax6 paired domain are regulated by alternative splicing.

Two independent and interactive DNA-binding subdomains of the Pax6 paired domain are regulated by alternative splicing.

The HNF1β transcription factor has several domains involved in nephrogenesis and partially rescues Pax8/lim1‐induced kidney malformations

Elements and factors involved in tissue-specific and embryonic expression of the liver transcription factor LFB1 in Xenopus laevis.

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