Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The transcription activator protein NtrC (nitrogen regulatory protein C) can catalyze the transition of E. coli RNA polymerase complexed with the sigma54 factor (RNAP.sigma54) from the closed complex (RNAP.sigma54 bound at the promoter) to the open complex (melting of the promoter DNA). This process involves phosphorylation of NtrC, assembly of a multimeric NtrC complex at the enhancer DNA sequence, interaction of this complex with promoter bound RNAP. sigma54 via DNA looping, and hydrolysis of ATP. We have used analytical ultracentrifugation to study the different NtrC association states and to derive hydrodynamic models for the conformation of the various NtrC species. The following results were obtained. (i) The unphosphorylated wild-type protein formed a dimer with a measured molecular weight of 102(+/-3) kDa, which compares to a calculated molecular weight of 54 kDa for a monomer (concentration range studied 2 to 8 microM NtrC monomer). (ii) In the unphosphorylated state one NtrC dimer was bound to one binding site as determined with DNA oligonucleotide duplexes containing one or two binding sites (concentration range studied 50 to 1000 nM NtrC dimer). (iii) The data obtained at protein concentrations that were below the concentration of binding sites indicate that binding to the DNA duplex with two binding sites occurred with essentially no cooperativity. The experiments were conducted in the absence of ATP. (iv) The phosphorylated protein formed a specific complex at the DNA duplex with the enhancer sequence (two NtrC binding sites) that consisted of four dimers (concentration range studied 100 to 1000 nM NtrC dimer). (v) The formation of this octameric complex was highly cooperative, and the data suggest that two DNA strands could bind simultaneously to this complex. (vi) From the sedimentation data a model was derived in which the NtrC dimer adopts a V shaped structure with the DNA binding domains being located at the bottom and the two receiver domains at the top of the V. In this conformation higher order NtrC complexes can be stabilized by interaction between the phosphorylated receiver domain and the central activation domain of different NtrC dimers.
J Mol Biol 1998 May 22
PMID:Association states of the transcription activator protein NtrC from E. coli determined by analytical ultracentrifugation. 960 Aug 53

Modulation of eukaryotic gene expression is influenced by the organization of regulatory DNA-elements in chromatin. The mouse mammary tumor virus (MMTV) promoter exhibits regularly positioned nucleosomes that reduce the accessibility of the binding sites for sequence-specific transcription factors, in particular nuclear factor (NF1). Hormonal induction of the MMTV promoter is accompanied by remodeling of the nucleosomal structure, but the biochemical nature of these structural changes is unknown. Using recombinant histones, we have now assembled the MMTV promoter in particles containing either an octamer of the histones H3, H4, H2A and H2B or a tetramer of histones H3 and H4, and have compared the two particles in terms of structure, positioning, and exclusion of transcription factors. Using site-directed hydroxy radicals to map histone locations, two main nucleosome positions are found with dyads at position -107 and at -127. The same two main positions are found for particles containing only the H3/H4 tetramer, showing that the absence of H2A/H2B dimers does not alter positioning. The rotational orientation of the DNA double helix in both types of particles is essentially identical. However, the ends of the nucleosomal DNA as well as its central region are more accessible to cleavage reagents in the tetramer particle than in the octamer particle. In agreement with these structural features, the transcription factors NF1 and OTF1 were able to bind to their cognate sites on the tetramer particle, while they could not gain access to the same sites on the surface of the octamer particle. The DNase I digestion pattern of octamers treated with partially purified SWI/SNF complex from HeLa cells in the presence of ATP is indistinguishable from that of tetramer particles, suggesting that the SWI/SNF complex promotes ATP-dependent remodeling of the octamer particle but not of tetramer particles. These results are compatible with a hormone-induced removal of histone H2A/H2B during MMTV induction.
J Mol Biol 1998 May 15
PMID:The mouse mammary tumour virus promoter positioned on a tetramer of histones H3 and H4 binds nuclear factor 1 and OTF1. 961 38

In the yeast Saccharomyces cerevisiae, the SWI-SNF complex has been proposed to antagonize the repressive effects of chromatin by disrupting nucleosomes. The SIN genes were identified as suppressors of defects in the SWI-SNF complex, and the SIN1 gene encodes an HMG1-like protein that has been proposed to be a component of chromatin. Specific mutations (sin mutations) in both histone H3 and H4 genes produce the same phenotypic effects as do mutations in the SIN1 gene. In this study, we demonstrate that Sin1 and the H3 and H4 histones interact genetically and that the C terminus of Sin1 physically associates with components of the SWI-SNF complex. In addition, we demonstrate that this interaction is blocked in the full-length Sin1 protein by the N-terminal half of the protein. Based on these and additional results, we propose that Sin1 acts as a regulatable bridge between the SWI-SNF complex and the nucleosome.
Mol Cell Biol 1998 Jul
PMID:The C-terminal domain of Sin1 interacts with the SWI-SNF complex in yeast. 963

Analysis of the DNA sequence of a 17 kb region of the coli lambdoid phage H-19B genome located the genes encoding shiga-like toxin I (Stx-I) downstream of the gene encoding the analogue of the phage lambda Q transcription activator with its site of action, qut at the associated pR' late promoter, and upstream of the analogues of lambda genes encoding lysis functions. Functional studies, including measurement of the effect of H-19B Q action on levels of Stx expressed from an H-19B prophage, show that the H-19B Q acts as a transcription activator with its associated pR'(qut) by promoting readthrough of transcription terminators. Another toxin-producing phage, 933W, has the identical Q gene and pR'(qut) upstream of the stx-II genes. The H-19B Q also activates Stx-II expression from a 933W prophage. An ORF in H-19B corresponding to the holin lysis genes of other lambdoid phages differs by having only one instead of the usual two closely spaced translation initiation signals that are thought to contribute to the time of lysis. These observations suggest that stx-I expression can be enhanced by transcription from pR' as well as a model for toxin release through cell lysis mediated by action of phage-encoded lysis functions. Functional studies show that open reading frames (ORFs) and sites in H-19B that resemble components of the N transcription antitermination systems controlling early operons of other lambdoid phages similarly promote antitermination. However, this N-like system differs significantly from those of other lambdoid phages.
Mol Microbiol 1998 Jun
PMID:Functional and genetic analysis of regulatory regions of coliphage H-19B: location of shiga-like toxin and lysis genes suggest a role for phage functions in toxin release. 968 Feb 14

Target genes for the helicase-like transcription factor (HLTF), a member of the SNF/SWI family, were immunoprecipitated from HeLa chromatin fragments with an anti-HLTF antibody. A 182 bp fragment ( HEFT1 ) presented 87% sequence identity with 3.3 kb dispersed repeats from the 4q35 D4Z4 locus linked to facioscapulohumeral muscular dystrophy (FSHD). The HEFT1 loci were, however, not genetically linked to FSHD. Transfection and in vitro binding studies identified within HEFT1 a promoter whose basal activity required a GC box activated by Sp1 or Sp3. A 4.4 kb homologous transcript was found mostly in human skeletal muscle and heart. A 1.2 kb cDNA fragment was cloned that encoded a 170 amino acid protein (DUX1) with two paired-type homeodomains. In vitro translated DUX1 specifically interacted in electrophoretic mobility shift assay (EMSA) with a P5 oligonucleotide (5'-GATCTGAGTCTAATTGAGAATTACTGTAC-3'). DUX1 co-expression activated up to 5-fold transient expression in insect cells of a minimal promoter-luciferase construct fused to P5. The presence of 20 kDa DUX1 in vivo in rhabdomyosarcoma TE671 cell extracts was shown by western blotting with a rabbit antiserum raised against a DUX1 peptide. This antiserum suppressed a TE671 protein-P5 complex in EMSA with identical migration as the in vitro translated DUX1-P5 complex. Genomic PCR experiments could not identify a gene fragment linking the HEFT1 and DUX1 sequences, which present one mismatch in their overlapping region. However, a similar gene was found in another 3.3 kb element comprising the HEFT1 promoter and a DUX1 -like open reading frame. In addition, homologous gene sequences were identified in 3.3 kb elements of the D4Z4/FSHD locus, considered until now 'junk' DNA.
Hum Mol Genet 1998 Oct
PMID:Characterization of a double homeodomain protein (DUX1) encoded by a cDNA homologous to 3.3 kb dispersed repeated elements. 973 70

Gene activation is often preceded by or accompanied by a perturbation of the chromatin structure. Recently, several co-factors of transcription factors have been identified as histone acetyltransferases. In addition, retinoblastoma protein and some co-factors can form a complex with histone deacetylases. These discoveries provide direct evidence that modification of chromatin structure is crucial for gene activation. However, the role of chromatin structure in cardiac-specific expression has not yet been elucidated. The potential significance of chromatin structure in cardiac-specific gene expression is indicated by: (1) heterogeneous human SWI/SNF chromatin remodelling factors among various tissues; (2) several chromatin remodelling factors shown to be expressed preferentially in the heart; (3) the demonstration of chromatin remodelling of the cardiac beta-myosin heavy chain gene (MyHC) during cardiac development. We therefore propose to study cardiac-specific chromatin remodelling activity in order to elucidate mechanisms controlling the reactivation of the fetal heart genetic program in the hypertrophic heart.
J Mol Cell Cardiol 1998 Sep
PMID:Chromatin structure and cardiac gene expression. 976 23

The yeast Saccharomyces cerevisiae contains two related chromatin-remodeling complexes, RSC and SWI/SNF, which are shown to share the actin-related proteins Arp7 and Arp9. Depending on the genetic background tested, arp7 delta and arp9 delta mutants are either inviable or show greatly impaired growth and Swi-/Snf- mutant phenotypes. Unlike swi/snf mutants, viable arp7 delta or arp9 delta mutants have an Spt- phenotype, suggesting that RSC affects transcription. Temperature-sensitive mutations in ARP7 and ARP9 were isolated, and the amino acid changes support the structural relationship of Arp7 and Arp9 to actin. However, site-directed mutations predicted to impair ATP binding or hydrolysis did not detectably affect Arp7 or Arp9 function. Our results suggest that actin-related proteins perform important roles in chromatin-remodeling complexes by virtue of structural rather than enzymatic similarities to actin.
Mol Cell 1998 Nov
PMID:Two actin-related proteins are shared functional components of the chromatin-remodeling complexes RSC and SWI/SNF. 984 36

Nuclear matrix attachment regions (MARs) flanking the immunoglobulin heavy chain intronic enhancer (Emu) are the targets of the negative regulator, NF-muNR, found in non-B and early pre-B cells. Expression library screening with NF-muNR binding sites yielded a cDNA clone encoding an alternatively spliced form of the Cux/CDP homeodomain protein. Cux/CDP fulfills criteria required for NF-muNR identity. It is expressed in non-B and early pre-B cells but not mature B cells. It binds to NF-muNR binding sites within Emu with appropriate differential affinities. Antiserum specific for Cux/CDP recognizes a polypeptide of the predicted size in affinity-purified NF-muNR preparations and binds NF-muNR complexed with DNA. Cotransfection with Cux/CDP represses the activity of Emu via the MAR sequences in both B and non-B cells. Cux/CDP antagonizes the effects of the Bright transcription activator at both the DNA binding and functional levels. We propose that Cux/CDP regulates cell-type-restricted, differentiation stage-specific Emu enhancer activity by interfering with the function of nuclear matrix-bound transcription activators.
Mol Cell Biol 1999 Jan
PMID:Cux/CDP homeoprotein is a component of NF-muNR and represses the immunoglobulin heavy chain intronic enhancer by antagonizing the bright transcription activator. 985 52

The genes of the trithorax group (trxG) in Drosophila melanogaster are required to maintain the pattern of homeotic gene expression that is established early in embryogenesis by the transient expression of the segmentation genes. The precise role of each of the diverse trxG members and the functional relationships among them are not well understood. Here, we report on the isolation of the trxG gene moira (mor) and its molecular characterization. mor encodes a fruit fly homolog of the human and yeast chromatin-remodeling factors BAF170, BAF155, and SWI3. mor is widely expressed throughout development, and its 170-kDa protein product is present in many embryonic tissues. In vitro, MOR can bind to itself and it interacts with Brahma (BRM), an SWI2-SNF2 homolog, with which it is associated in embryonic nuclear extracts. The leucine zipper motif of MOR is likely to participate in self-oligomerization; the equally conserved SANT domain, for which no function is known, may be required for optimal binding to BRM. MOR thus joins BRM and Snf5-related 1 (SNR1), two known Drosophila SWI-SNF subunits that act as positive regulators of the homeotic genes. These observations provide a molecular explanation for the phenotypic and genetic relationships among several of the trxG genes by suggesting that they encode evolutionarily conserved components of a chromatin-remodeling complex.
Mol Cell Biol 1999 Feb
PMID:The trithorax group gene moira encodes a brahma-associated putative chromatin-remodeling factor in Drosophila melanogaster. 989 Oct 50

SWI-SNF complexes have been implicated in transcriptional regulation by chromatin remodeling. We have identified an interaction between two components of the mammalian SWI-SNF complex and cyclin E, an essential cell cycle regulatory protein required for G1/S transition. BRG1 and BAF155, mammalian homologs of yeast SWI2 and SWI3, respectively, are found in cyclin E complexes and are phosphorylated by cyclin E-associated kinase activity. In this report, we show that overexpression of BRG1 causes growth arrest and induction of senescence-associated beta-galactosidase activity, which can be overcome by cyclin E. Our results suggest that cyclin E may modulate the activity of the SWI-SNF apparatus to maintain the chromatin in a transcriptionally permissive state.
Mol Cell Biol 1999 Feb
PMID:Cyclin E associates with BAF155 and BRG1, components of the mammalian SWI-SNF complex, and alters the ability of BRG1 to induce growth arrest. 989 Oct 79


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>