Developmental regulation and tissue distribution of the liver transcription factor LFB1 (HNF1) in Xenopus laevis.

Bartkowski, S; Zapp, D; Weber, Heike; Eberle, G; Zoidl, Christiane; Senkel, Sabine; Klein-Hitpaß, Ludger; Ryffel, Gerhart U.

doi:10.1128/mcb.13.1.421

Cited by 42 publications

(30 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To prepare a model RNA template for the newt ribozyme, a partial sequence encoding the N-terminal part of the Xenopus liver transcription factor 1 (XLFBI) [9] was excised with EcoRI from the plasmid pBSlll (kindly provided by R. Vignali, Pisa). The digest was separated by electrophoresis on a 1% agarose gel and a fragment of approximately 1000 bp representing the XLFBI partial cDNA was isolated and ligated into the EcoRI site of the plasmid pGEM7Zf( +).…”

Section: Methodsmentioning

confidence: 99%

Intermolecular Cleavage by the Newt Ribozyme

Marusic

Luzi

Barsacchi

et al. 1997

European Journal of Biochemistry

View full text Add to dashboard Cite

To analyse the trans-cleavage activity of the hammerhead ribozyme occurring in the ovary of the newt (Notophthalmus, Triturus) in more detail, six synthetic ribozymes representing natural and modified hammerhead sequences were tested with both short oligoribonucleotides and long transcripts as substrates. The same analysis was also performed with the monomer (330 nucleotides) newt ribozyme and variants thereof. None of the ribozymes comprising the newt natural sequence showed activity under multiple turnover conditions, regardless of sequence changes in stem and loop 11. With excess of ribozyme, the same ribozymes cleaved only to a limited extent a short substrate and extremely poorly a target site embedded within a long transcript. The addition of whole ovary cell extract had little influence on cleavage activity of short substrates. However, sequence changes in stems I and 111 to target different sequences considerably improved cleavage ability of the ribozymes under all conditions used. An RNA secondarystructure folding program showed that ribozymes with the natural newt sequence did not fold in a hammerhead structure whereas those with the changes in stem I and 111 did. These results suggest that the sequence of the stems I and 111 impairs the assembly of the newt ribozyme into a bimolecular hammerhead complex in vitro and that proteins present in the ovaries do not facilitate activity.Keywords: catalytic RNA ; hammerhead ; trans-cleavage; RNA-binding protein.A family of highly repetitive DNA sequences, dispersed in small clusters in the newt (Notophthalmus, Triturus) genome, codes for stable, strand-specific transcripts found in both somatic and germinal tissues ([l] and Cremisi, F., personal communication). The transcripts correspond in size precisely to monomeric (330 bp) and multimeric DNA repeat units. Evidence that synthetic dimer-rize transcripts undergo site-specific, selfcatalyzed cleavage in vitro suggested that the same reaction might be involved in the processing of large multimeric transcripts in vivo 12, 31. The self-cleavage reaction requires Mg" and occurs within a conserved structure named the hammerhead, similar to that of infectious plant RNAs [4].The ovarian ribozyme transcripts differ from the analogous transcripts in other newt tissues in having an intact self-cleavage site, located about SO nucleotides from the 5' end [2]. Therefore, it seems that monomer length transcripts of the ovarian newt ribozyme ,are more likely to arise rather from trancription than from self-processing by cleavage. It has indeed been shown that the same promoter elements that regulate polymerase-11-dependent transcription of small nuclear RNAs are involved in transcription of the newt ribozyme [5, 61. The presence of an apparently functional gene that codes for the small RNA with a hammerhead domain suggests that a biological function of this particular ribozyme may be trans-cleavage of a specific, but still unknown RNA target in vivo [5, 61. Here we report an in vitro study of the trans-cleaving properties o...

show abstract

Section: Methodsmentioning

confidence: 99%

Intermolecular Cleavage by the Newt Ribozyme

Marusic

Luzi

Barsacchi

et al. 1997

European Journal of Biochemistry

View full text Add to dashboard Cite

show abstract

“…(C) Schematic representation of LFBl and LFB1-VP16-ER. The domain structure of LFBl is indicated above the scheme according to Bartkowski et al (1993). In the fusion protein LFBl-VP16-ER, the black bar marked VP16 represents the activation domain (amino acids 411 -487) of the viral protein-16 (Triezenberg et al, 1988).…”

Section: Construction Of Hormone-dependent Derivatives Of the Transcrmentioning

confidence: 99%

“…acid dimerization domain, a DNA-binding domain with homologies to POU and homeodomain proteins and several activation domains at the C-terminus (Tronche and Yaniv, 1992;Bartkowski et al, 1993; Fig. 1C).…”

Section: Construction Of Hormone-dependent Derivatives Of the Transcrmentioning

confidence: 99%

“…According to their DNA-binding specificity, these transcription factors were subdivided into the liver factor B 1 (LFBl), hepatocyte nuclear factor-3 (HNF3), hepatocyte nuclear factor-4 (HNF4), or CCAAT bodenhancerbinding protein (CEBP) families (Xanthopoulos and Mirkovitch, 1993). Using the cloned cDNA and antibodies, it was established that these factors are not restricted to the liver but are also found in other tissues Bartkowski et al, 1993). One approach to understand the role of these tissue-specific transcription factors within a certain cell type and in differentiation and embryogenesis is to introduce these factors into cells in which they are normally not expressed.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Estrogen‐Inducible Derivatives of Hepatocyte Nuclear Factor‐4, Hepatocyte Nuclear Factor‐3 and Liver Factor B1 are Differently Affected by Pure and Partial Antiestrogens

Drewes

Clairmont

Klein-Hitpaß

et al. 1994

European Journal of Biochemistry

View full text Add to dashboard Cite

The tissue-specific transcription factors of the hepatocyte nuclear factor-4 (HNF4), hepatocyte nuclear factor-3 (HNF3), and liver factor B1 (LFB1) families are thought to play a role in the development of internal organs and in the tissue-specific expression of many distinct genes. We have now constructed derivatives of these proteins by introducing the hormone-binding domain of the estrogen receptor and show that in transient transfections these chimeric proteins act as estrogeninducible transcription factors with the DNA sequence specificity of the original factors. These chimeric transcription factors are differently affected by the partial estrogen antagonist 4-hydroxytamoxifen and the pure antiestrogen N-n-butyl-ll-(3,17-dihydroxy-estra-l,3,5(1O)-trien-7a-yl)Nmethyl-undecamide (ICI 164384) ; 4-hydroxytamoxifen activates, at least partially, all the chimeric factors and the estrogen receptor, while ICI 164384 surprisingly activates the transcription factors derived from HNF3 and LFBl and inhibits only the estrogen receptor and the HNF4 derivative. Together with the DNA-sequence-binding specificity, the different response to estrogen and antiestrogens makes our estrogen receptor fusion proteins useful tools for the investigation of the roles of HNF4, HNF3 and LFBl in gene expression, differentiation and developmental processes.Over the last decade, the investigation of the mechanisms involved in liver-specific gene expression has led to the identification first of DNA elements responsible for this tissue specificity and subsequently of protein factors which are able to bind specifically to these promoter elements. Many of these factors have recently been cloned and shown to be transcriptional activators of reporter genes containing DNA elements that mediate liver-specific gene expression (Lai and Darnell, 1991;Sladek and Darnell, 1992;Xanthopoulos and Mirkovitch, 1993). According to their DNA-binding specificity, these transcription factors were subdivided into the liver factor B 1 (LFBl), hepatocyte nuclear factor-3 (HNF3), hepatocyte nuclear factor-4 (HNF4), or CCAAT bodenhancerbinding protein (CEBP) families (Xanthopoulos and Mirkovitch, 1993). Using the cloned cDNA and antibodies, it was established that these factors are not restricted to the liver but are also found in other tissues Bartkowski et al., 1993). One approach to understand the role of these tissue-specific transcription factors within a certain cell type and in differentiation and embryogenesis is to introduce these factors into cells in which they are normally not expressed. As it has been shown that estrogen- N-n-butyl-ll-(3,17-dihydroxy-estra-l,3,5(10)-trien-7a-yl)N-methyl-undecamide; LFB1, liver factor B1; VP, viral protein.inducible fusion proteins of transcription factors containing the hormone-binding domain of the estrogen receptor are useful tools to investigate the role of transcription factors in these processes (Umek et al., 1991 ;Burk and Klempnauer, 1991 ;Briegel et al., 1993), we decided to establish estrogendependent deriva...

show abstract

“…In vertebrate development, both transcription factors are expressed in defined embryonic regions including the developing kidney. In mammals (5-7) as well as in Xenopus (8,9), the expression of HNF1␤ precedes the appearance of HNF1␣. HNF1␤-deficient mouse embryos die soon after implantation with poorly organized ectoderm and no discernible visceral or parietal endoderm (10,11).…”

mentioning

confidence: 99%

The mutated human gene encoding hepatocyte nuclear factor 1β inhibits kidney formation in developing Xenopus embryos

Wild

Strandmann

Nastos

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The transcription factor hepatocyte nuclear factor 1␤ (HNF1␤) is a tissue-specific regulator that also plays an essential role in early development of vertebrates. In humans, four heterozygous mutations in the HNF1␤ gene have been identified that lead to early onset of diabetes and severe primary renal defects. The degree and type of renal defects seem to depend on the specific mutation. We show that the frameshift mutant P328L329fsdelCCTCT associated with nephron agenesis retains its DNA-binding properties and acts as a gain-of-function mutation with increased transactivation potential in transfection experiments. Expression of this mutated factor in the Xenopus embryo leads to defective development and agenesis of the pronephros, the first kidney form of amphibians. Very similar defects are generated by overexpressing in Xenopus the wild-type HNF1␤, which is consistent with the gain-of-function property of the mutant. In contrast, introduction of the human HNF1␤ mutant R137-K161del, which is associated with a reduced number of nephrons with hypertrophy of the remaining ones and which has an impaired DNA binding, shows only a minor effect on pronephros development in Xenopus. Thus, the overexpression of both human mutants has a different effect on renal development in Xenopus, reflecting the variation in renal phenotype seen with these mutations. We conclude that mutations in human HNF1␤ can be functionally characterized in Xenopus. Our findings imply that HNF1␤ not only is an early marker of kidney development but also is functionally involved in morphogenetic events, and these processes can be investigated in lower vertebrates.

show abstract

Developmental regulation and tissue distribution of the liver transcription factor LFB1 (HNF1) in Xenopus laevis.

Cited by 42 publications

References 50 publications

Intermolecular Cleavage by the Newt Ribozyme

Intermolecular Cleavage by the Newt Ribozyme

Estrogen‐Inducible Derivatives of Hepatocyte Nuclear Factor‐4, Hepatocyte Nuclear Factor‐3 and Liver Factor B1 are Differently Affected by Pure and Partial Antiestrogens

The mutated human gene encoding hepatocyte nuclear factor 1β inhibits kidney formation in developing Xenopus embryos

Contact Info

Product

Resources

About