Structural homology of the product of the Drosophila Krüppel gene with Xenopus transcription factor IIIA

Rosenberg, Urs B.; Schröder, Christian; Preiss, Anette; Kienlin, Andrea; Côté, Serge; Riede, Isolde; Jäckle, Herbert

doi:10.1038/319336a0

Cited by 454 publications

(234 citation statements)

References 33 publications

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“…ADR1 contains two zinc finger domains (10), similar to those which were first observed in transcription factor IIIA from Xenopus laevis, having the consensus sequence Cys-X24-Cys-X3-Phe-X5-Leu-X2-His-X2-His (5, 19). Zinc finger domains have since been found in several eucaryotic genes thought to be involved in the regulation of transcription (6,18,25,29,30) and in some cases have been shown to bind DNA specifically at regulatory elements (8,15,28). Point mutations in either finger region of ADR1 can give rise to null mutants which are incapable of activating ADH2 expression (3).…”

mentioning

confidence: 99%

The yeast regulatory protein ADR1 binds in a zinc-dependent manner to the upstream activating sequence of ADH2.

Eisen¹,

Taylor²,

Blumberg³

et al. 1988

Mol. Cell. Biol.

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The yeast ADR1 protein contains two zinc finger domains that are essential for its role in transcriptional activation of alcohol dehydrogenase (ADH2). These domains are thought to function as DNA-binding structures. An ADR1-,B-galactosidase fusion protein made in Escherichia coli and containing the finger domains of ADR1 binds in vitro in a zinc-dependent manner to DNA fragments containing the two ADH2 upstream activation sequences. The strongest binding is to upstream activation sequence 1, a 22-base-pair palindrome.ADR1 is a nuclear protein which is necessary for transcription of the glucose-repressible alcohol dehydrogenase gene (ADH2) in the yeast Saccharomyces cerevisiae. Repression of ADH2 is apparently maintained by posttranslational regulation of ADR1 (4, 7) rather than by DNA-binding repressors (14). The promoter of ADH2 requires upstream activation sequences (UAS) composed of two elements which function synergistically. UAS1 is a 22-base-pair (bp) inverted repeat which allows ADR1-dependent derepression of ADH2 (27). The UAS2 sequence includes the 25 bp directly upstream of UAS1 and allows ADR1-independent derepression of ADH2 expression (J. Yu, personal communication). ADR1 contains two zinc finger domains (10), similar to those which were first observed in transcription factor IIIA from Xenopus laevis, having the consensus sequence Cys-X24-Cys-X3-Phe-X5-Leu-X2-His-X2-His (5, 19). Zinc finger domains have since been found in several eucaryotic genes thought to be involved in the regulation of transcription (6,18,25,29,30) and in some cases have been shown to bind DNA specifically at regulatory elements (8,15,28). Point mutations in either finger region of ADR1 can give rise to null mutants which are incapable of activating ADH2 expression (3). To understand how ADR1 and other finger proteins bind DNA, we studied the in vitro DNAbinding properties of an ADR1-p-galactosidase fusion protein expressed in Escherichia coli.Binding of ADR1-P-galactosidase to the UAS of ADH2. A polypeptide containing amino acids 17 through 229 of ADR1 fused to P-galactosidase (H. Blumberg, Ph.D. thesis, University of Washington, Seattle, 1987), ADR1-229Z, was expressed in E. coli under the control of the strong, heatinducible A promoter, PR, on plasmid pCQ-A229Z (Fig. 1A) (23). Western blot (immunoblot) analysis of extracts with an anti-3-galactosidase antibody showed that 50% of the fusion protein was proteolyzed to B-galactosidase (data not shown). To investigate ADR1 binding to the ADH2 promoter, gel retardation analysis was performed with crude cell extracts of ADR1-229Z mixed with radiolabeled DNA fragments of the ADH2 promoter (Fig. 1B). Protein-DNA complexes of ADR1-229Z bound to radiolabeled promoter DNA are shown in Fig. 2.

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mentioning

confidence: 99%

The yeast regulatory protein ADR1 binds in a zinc-dependent manner to the upstream activating sequence of ADH2.

Eisen¹,

Taylor²,

Blumberg³

et al. 1988

Mol. Cell. Biol.

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“…Nevertheless, the similarity in DNA-protein interaction may indicate a common structural organization and even similarity in the mode of action of the two factors. It is worth noting in this respect that several other eukaryotic regulatory proteins were found to have fingerlike domains (6), in species as distant as yeast (46) and Drosophila (47). PEB1 factor may thus be the first enhancer factor belonging to this larger family of DNA binding proteins.…”

Section: Discussionmentioning

confidence: 99%

Molecular analysis of the interaction between an enhancer binding factor and its DNA target

Piette

Yaniv

1986

Nucl Acids Res

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ABSTRATTIei fine contacts of a mouse nuclear factor, called PEB1, with the B enhancer of polyoma virus were analyzed. It protects against DNaseI attack a region of about 50 base pairs that can be divided in two domains. The first contains a GC-rich palindrome and the homology to the SV40 enhancer. The second is homologous to a sequence in the immunoglobulin (Ig) heavy chain gene enhancer. Methylation interference and protection experiments reveal strong specific contacts only with a purine rich track on the late coding strand of the early proximal part of the palindrome. Deletion analysis show that the minimal sequences necessary for binding include only the first domain. The Ig homology contributes only weakly to the binding. The minimal core is similar to the core of the B enhancer defined in vivo. The interactions we observe here are reminiscent of those of TFIIIA positive transcription factor and the 5SRNA gene of Xenopus. INTKRODUIONDNA-protein interactions play an essential role in the regulation of gene expression and DNA replication. Characterization of these interactions can help unravel the mechanisms involved in these processes. Repressor-operator interactions in prokaryotes were the first to be analyzed in great detail: in essence, a repressor dimer interacts with both parts of a palindromic sequence in a symmetric way; a conserved c-helix-turn-a-helix motif fits into the large groove of right-handed B-DNA (1). This model was found to be applicable to activator proteins like the CAP protein (2) or even yeast proteins involved in mating type control (3).In higher eukaryotes only a few cases of specific DNA-protein interactions have been studied in detail so far. The positive transcription factor TF III A of Xenopus laevis contacts the DNA mainly along the non coding strand (4) and the helical configuration of the DNA may be altered by this binding (5). Knowledge of the primary structure of the protein has led to a model in which small Zn++ binding, fingerlike domains interact with the DNA in a way quite different from bacterial repressors or activators (6). Another

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“…When the first segmentation and homeotic mutations were cloned, it was recognized that they shared certain sequence motifs, i.e. the homeo box (Gehring and Hiromi, 1986), paired box (Bopp et al, 1986) or zincfinger structure (Rosenberg et al, 1986) and that they could act as transcriptional regulators. These motifs were also shown to be evolutionarily conserved from insects to mammals.…”

Section: Transcriptional Regulatorsmentioning

confidence: 99%

“…This group of genes contains zinc-finger DNA-binding motifs as a common element. Numerous genes have been isolated based on sequence similarity to the Drosophila gap gene Kriippel (Chowdhury et al, 1987;Rosenberg et al, 1986) but no indication for a specific role during development has been demonstrated (El-Baradi et al, 1991).…”

Section: Transcriptional Regulatorsmentioning

confidence: 99%

The molecular and genetic analysis of mouse development

Gossler¹,

Balling

1992

European Journal of Biochemistry

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This review describes some recent advances in the molecular‐genetic analysis of mouse development. Reversed genetics and gene assignment have been used to isolate genes affected in developmental mutations. The establishment of a high‐density molecular‐genetic map promises to facilitate cloning of additional genes with developmental functions. Based on molecular, biochemical or other biological criteria many mouse genes that code for transcriptional regulators, growth‐factor‐like molecules and their receptors have been isolated. The role of these genes during development can be analysed in vivo after producing targeted mutations. Mutations can be generated by homologous recombination in the genome of embryonic stem cells and can then be introduced into the mouse germ line by means of germ‐line chimaeras. Additional approaches employing stem cells to identify and mutate putative developmental genes are coming into use.

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Structural homology of the product of the Drosophila Krüppel gene with Xenopus transcription factor IIIA

Cited by 454 publications

References 33 publications

The yeast regulatory protein ADR1 binds in a zinc-dependent manner to the upstream activating sequence of ADH2.

The yeast regulatory protein ADR1 binds in a zinc-dependent manner to the upstream activating sequence of ADH2.

Molecular analysis of the interaction between an enhancer binding factor and its DNA target

The molecular and genetic analysis of mouse development

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