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At least 1,603 records · Page 89Linked to original sources
PubMed1984

Transcriptional and post-transcriptional control of specific messenger RNAs in adult and embryonic liver.

The rate of synthesis and the concentrations of a variety of messenger RNA sequences have been compared between adult mouse liver cells and cells in other adult tissues, and between cells in fetal and neonatal liver. The sequences were distinguished as "liver-specific" or "common" in a previous report, where liver was compared with brain cells and cultured cells. Most of the liver-specific mRNAs are greatly decreased or absent in a large group of other adult mouse tissues. In two cases, kidney shares mRNA sequences with liver. The levels of the common mRNAs varied from two to fivefold in various tissues. For the liver-specific mRNAs, the transcription rates in nuclei from adult tissues and from fetal liver showed a good correspondence to the presence and the level of mRNA. However, most of the common RNA sequences were transcribed at similar rates in all nuclei despite their different cytoplasmic concentrations. In addition, two liver-specific RNAs were transcribed in fetal liver nuclei but were not present as mRNA. Thus, the presence of tissue-specific mRNAs in adult cells is based first (and probably most importantly) on transcriptional control, but several instances were observed where post-transcriptional control also contributes to the level of mRNA.

Aging↗
PubMed2004

Elicitor-induced activation of transcription via W box-related cis-acting elements from a basic chitinase gene by WRKY transcription factors in tobacco.

A putative elicitor responsive element with two W boxes (CTGACC/T) has been identified in the region between -125 and -69 of a tobacco class I basic chitinase gene CHN48. We generated transgenic tobacco calli that contained the -125/-69 region fused to a luciferase reporter gene. The expression of the reporter gene was induced upon treatment with an elicitor, xylanase from Trichoderma viride (TvX). This induction required protein kinase activity. We isolated three cDNA clones encoding DNA-binding proteins, designated as NtWRKY1, NtWRKY2, and NtWRKY4, from tobacco cultured cells. Gel mobility shift assays showed that in vitro translation products of NtWRKY1, NtWRKY2 and NtWRKY4 bound to W box of CHN48 gene. These NtWRKY proteins stimulated W box-mediated transcription of a luciferase reporter gene in the transient assay. In addition, the transactivation of W box-mediated transcription by NtWRKY1 and NtWRKY4 was enhanced in response to elicitor treatment, suggesting elicitor-induced posttranscriptional activation of these NtWRKYs. Northern blot analyses showed that mRNAs for NtWRKY1 and NtWRKY2 increased after treatment with the elicitor, whereas mRNAs for NtWRKY4 were expressed constitutively at a low level. These results suggested possible involvement of NtWRKYs in elicitor-responsive transcription of defense genes in tobacco.

Amino Acid Sequence↗
PubMed2004

Controlled transcriptional regulation in eukaryotes by a novel transcription factor derived from Escherichia coli purine repressor.

Unlike the DNA-binding domains (DBD) of most eukaryotic transcription factors, Escherichia coli LacI family transcription factors are unable to bind to specific target DNA sequences without a cofactor-binding domain. In the present study, we reconstructed a novel DBD designated as PurHG, which binds constitutively to a 16bp purine repressor operator, by fusion of the purine repressor (PurR) DBD (residues 1-57) and the GAL4 dimerization domain (DD, residues 42-148). Binding of PurHG to DNA requires the dimerization and a hinge helix of PurR DBD. When the PurHG was expressed as a fusion protein in a form of a transcription activator (PurAD) or an artificial nuclear receptor (PurAPR or PurAER) responding to ligand, such as RU486 or beta-estradiol, it could regulate the expression of the reporter genes in NIH3T3 cells. The prerequisite region of the GAL4 DD for DNA-binding was amino acid residues from 42 to 98 in the form of PurAD, while the amino acid residues from 42 to 75 were sufficient for ligand-dependent regulation in the form of PurAPR. These results suggest that the dimerization function of the progesterone ligand-binding domain could be substituted for region 76-98 of the GAL4 DD. In summary, the fusion of the PurR DBD and the GAL4 DD generates fully active DNA-binding protein, PurHG, in vitro and in vivo, and these results provide the direct evidence of structural predictions that the proximate positioning of PurR hinge helical regions is critical for DNA-binding.

Base Sequence↗
PubMed2005

Transcriptional feedback of Neurospora circadian clock gene by phosphorylation-dependent inactivation of its transcription factor.

The circadian clock protein Frequency (FRQ) feedback-regulates its own expression by inhibiting its transcriptional activator, White Collar Complex (WCC). We present evidence that FRQ regulates the bulk of WCC through modulation of its phosphorylation status rather than via direct complex formation. In the absence of FRQ, WCC is hypophosphorylated and transcriptionally active, while WCC is hyperphosphorylated and transcriptionally inactive when FRQ is expressed. The phosphorylation status of WCC changes rhythmically over a circadian cycle. Dephosphorylation and activation of WCC depend on protein phosphatase 2A (PP2A), and WCC is a substrate of PP2A in vitro. Hypophosphorylated WCC binds to the clock box of the frq promoter even in the presence of FRQ, while binding of hyperphosphorylated WCC is compromised even when FRQ is depleted. We propose that negative feedback in the circadian clock of Neurospora is mediated by FRQ, which rhythmically promotes phosphorylation of WCC, functionally equivalent to a cyclin recruiting cyclin-dependent kinase to its targets.

Circadian Rhythm↗
PubMed2006

Human transcription factors contain a high fraction of intrinsically disordered regions essential for transcriptional regulation.

Human transcriptional regulation factors, such as activators, repressors, and enhancer-binding factors are quite different from their prokaryotic counterparts in two respects: the average sequence in human is more than twice as long as that in prokaryotes, while the fraction of sequence aligned to domains of known structure is 31% in human transcription factors (TFs), less than half of that in bacterial TFs (72%). Intrinsically disordered (ID) regions were identified by a disorder-prediction program, and were found to be in good agreement with available experimental data. Analysis of 401 human TFs with experimental evidence from the Swiss-Prot database showed that as high as 49% of the entire sequence of human TFs is occupied by ID regions. More than half of the human TFs consist of a small DNA binding domain (DBD) and long ID regions frequently sandwiching unassigned regions. The remaining TFs have structural domains in addition to DBDs and ID regions. Experimental studies, particularly those with NMR, revealed that the transactivation domains in unbound TFs are usually unstructured, but become structured upon binding to their partners. The sequences of human and mouse TF orthologues are 90.5% identical despite a high incidence of ID regions, probably reflecting important functional roles played by ID regions. In general ID regions occupy a high fraction in TFs of eukaryotes, but not in prokaryotes. Implications of this dichotomy are discussed in connection with their functional roles in transcriptional regulation and evolution.

Animals↗
PubMed2002

Induction and superinduction of 2,3,7,8-tetrachlorodibenzo-rho-dioxin-inducible poly(ADP-ribose) polymerase: role of the aryl hydrocarbon receptor/aryl hydrocarbon receptor nuclear translocator transcription activation domains and a labile transcription repressor.

The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces a novel poly(ADP-ribose) polymerase (TiPARP). In this study, the signaling pathway of the induction was analyzed. Induction of TiPARP by TCDD occurs in both hepa1c1c7 cells and C57 mouse liver. Induction is concentration and time dependent. Genetic analyses reveal that induction is abolished in aromatic hydrocarbon receptor (AhR)- or aromatic hydrocarbon receptor nuclear translocator (Arnt)-defective variants but restored upon reconstitution of the variant cells with cDNAs expressing functional AhR or Arnt. Moreover, induction is largely reduced in cells expressing a deletion mutant of AhR or Arnt lacking the transcription activation (TA) domain, thus implicating the TA activities of both AhR and Arnt in the induction. Inhibition of protein synthesis by cycloheximide enhances the induction of TiPARP in the presence of an AhR agonist. The superinduction is transcriptional and does not require pretreatment with TCDD. Finally, inhibition of the 26S proteasomes by MG132 superinduces TiPARP. These findings establish that induction of TiPARP by TCDD is mediated through an AhR and Arnt transcription activation-dependent signal transduction that is repressed by a labile factor through the ubiquitin-26S proteasome-mediated protein degradation.

Animals↗
PubMed2002

Transcription of Xanthomonas campestris prt1 gene encoding protease 1 increases during stationary phase and requires global transcription factor Clp.

Xanthomonas campestris pv. campestris produces three proteases, Prt1, Prt2, and Prt3, the first two of which are involved in pathogenicity. In this study, nucleotide A 84 nt upstream of the prt1 start codon, which is 8 nt downstream of the -10 sequence, was determined as the transcription start site by the 5(') RACE (rapid amplification of cDNA ends) method. Using Pprt1-lacZ transcriptional fusion constructs for assays, several interesting characteristics of prt1 promoter were revealed. The expression is inducible by LB medium or casein proteins and involves the global transcription factor Clp (cyclic AMP receptor protein-like protein). The region containing bp -392 to -80 relative to the prt1 translation initiation codon is required for maximal expression, in which bp -392 to -207 responds to the Clp-mediated regulation and the induction. In presence of inducers and the clp wild-type background, the levels of expression continue to increase following cell growth until 30 h after the cultures entering stationary phase. Since prt1 promoter shows no response to stressful conditions and neither growth nor cell viability is affected by prt1 mutation, Prt1 appears to be a secondary metabolite of X. campestris pv. campestris.

5' Flanking Region↗
PubMed1986

Transcriptional and post-transcriptional roles of glucocorticoid in the expression of the rat 25,000 molecular weight casein gene.

In the presence of hydrocortisone, plus insulin and prolactin, rat mammary explants transcribe the 25K casein gene, and the half-life of the transcript is about 20 h. The first detectable effect of the withdrawal of glucocorticoid is reduction of the half-life of the casein mRNA to about 1 h, with full retention of the rate of transcription of the casein gene. A later effect of the withdrawal of glucocorticoid is loss of the ability to transcribe the casein gene. Both aberrations can be rectified by hydrocortisone in vitro. The instability of the 25K casein mRNA in the absence of glucocorticoid appears to be related to degradation in the nucleus. Accumulation of actin mRNA in the nuclear fraction is not dependent on glucocorticoid. The results indicate that glucocorticoid exerts a profound, selective effect on the stabilization of rat 25K casein mRNA, and is essential for the transcription of the casein gene. These effects can be dissociated temporally from one another.

Adrenalectomy↗
PubMed1999

The ubiquitous transcription factor NF-Y positively regulates the transcription of human p27Kip1 through a CCAAT box located in the 5-upstream region of the p27Kip1 gene.

Abnormally low levels of the cyclin-dependent kinase inhibitor p27Kip1 are found frequently in human carcinomas, and these levels correlate directly with both histological aggressiveness and patient mortality. p27Kip1 is haplo-insufficient for tumor suppression. Thus, p27Kip1 may be a useful molecule for the development of cancer therapies. To know the possible mechanisms underlying transcriptional control, we previously cloned the promoter region of human p27Kip1 gene. We report here the characterization of the 5'-regulatory region of the human p27Kip1 gene. Promoter analysis using 5'-deletion mutants revealed that a 39-bp region between -549 and -511 was required for maximal promoter activity. Point mutation analysis revealed that a CCAAT box within this region was essential for promoter activity. Gel shift assays and cotransfection experiments using a dominant negative form of the NF-Y transcription factor showed that NF-Y directly regulates p27Kip1 transcription through this CCAAT box. This finding might provide a clue to approach the mechanism of tumorigenesis.

Base Sequence↗
PubMed2003

Progesterone receptor transcription and non-transcription signaling mechanisms.

The diverse effects of progesterone on female reproductive tissues are mediated by the progesterone receptor (PR), a member of the nuclear receptor family of ligand-dependent transcription factors. Thus, PR is an important therapeutic target in female reproduction and in certain endocrine dependent cancers. This paper reviews our understanding of the mechanism of action of the most widely used PR antagonist RU486. Although RU486 is a competitive steroidal antagonist that can displace the natural hormone for PR, it's potency derives from additional "active antagonism" that involves inhibiting the activity of PR hormone agonist complexes in trans through heterodimerization and competition for binding to progesterone response elements on target DNA, and by recruitment of corepressors that have the potential to actively repress gene transcription. An additional functional role for PR has recently been defined whereby a subpopulation of PR in the cytoplasm or cell membrane is capable of mediating rapid progesterone induced activation of certain signal transduction pathways in the absence of gene transcription. This paper also reviews recent results on the mechanism of the extra-nuclear action of PR and the potential biological roles and implications of this novel PR signaling pathway.

Animals↗
PubMed1999

Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription.

MEN1 is a tumor suppressor gene that encodes a 610 amino acid nuclear protein (menin) of previously unknown function. Using a yeast two-hybrid screen with menin as the bait, we have identified the transcription factor JunD as a direct menin-interacting partner. Menin did not interact directly with other Jun and Fos family members. The menin-JunD interaction was confirmed in vitro and in vivo. Menin repressed transcriptional activation mediated by JunD fused to the Gal4 DNA-binding domain from a Gal4 responsive reporter, or by JunD from an AP1-responsive reporter. Several naturally occurring and clustered MEN1 missense mutations disrupted menin interaction with JunD. These observations suggest that menin's tumor suppressor function involves direct binding to JunD and inhibition of JunD activated transcription.

Animals↗
PubMed2004

Transcriptional control of the human pregnancy-specific glycoprotein 5 gene is dependent on two GT-boxes recognized by the ubiquitous specificity protein 1 (Sp1) transcription factor.

Pregnancy-specific glycoprotein 5 gene (PSG-5) belongs to the human pregnancy-specific glycoprotein family, encoded by eleven highly similar and transcriptionally active genes. High levels of PSG biosynthesis are restricted to the placenta syncytiotrophoblast and are essential for the maintenance of normal gestation in mammalian species. We have investigated here the nature of the transcription factors that recognize the FP1 (-455/-433) and the CPE (-147/-140) regulatory sequences that significantly contribute to basal PSG-5 promoter activity. Both elements bear a similar GT-box motif; and DNA-protein complex formation, as well as promoter activity, is largely dependent on the integrity of these GT-box sequences. Gel shift, super gel shift and UV-crosslinking experiments clearly demonstrate that the ubiquitous specificity protein 1 (Sp1) is the major transcription factor involved in complex formation with both cis-acting elements in normal term placenta tissue and in PSG-non-expressing COS-7 cells. Furthermore, transfection experiments indicate that Sp1 activates PSG-5 promoter constructs. In addition, we show that Sp1 is indeed co-expressed with PSG genes in the syncytiotrophoblast cells, stressing its potential role in the in vivo regulation of PSG expression.

Animals↗
PubMed1996

Transcriptional and post-transcriptional regulation of rainbow trout estrogen receptor and vitellogenin gene expression.

Estrogen receptor (ER) and vitellogenin (Vg) gene expression are strongly up-regulated by estrogens in rainbow trout liver. In this paper, we have used primary cultured hepatocytes to examine the mechanisms implicated in estrogen regulation of ER and Vg gene expression. Treatment of hepatocytes with 1 microM estradiol (E2) led to a rapid increase in ER and mRNA level (15 fold) followed by Vg and mRNA induction. Transcription rate and mRNA half-life determination carried out in the presence or absence of E2, demonstrated that E2 increases both the ER and Vg gene transcriptional activity and mRNA stability (ca. 3 fold). The effect of E2 was inhibited by an excess of antiestrogen, showing that E2-stimulation of ER and mRNA level is mediated by the estrogen receptor. Our data show that ER and Vg genes have different hormonal sensitivity. In fact, the Vg gene required a higher concentration of E2 to be stimulated compared to the ER gene. Examination of the mechanisms involved in post-transcriptional regulation of ER mRNA showed that the setting up and maintenance of this regulation process implies that estrogen receptor and the general translational activity within the cells, suggesting that ER mRNA depends on the synthesis of an estrogen-dependent protein. However, the cis and trans elements involved in E2-stabilization process remain to be identified.

Animals↗
PubMed2004

Constitutive expression of the AP-1 transcription factors c-jun, junD, junB, and c-fos and the marginal zone B-cell transcription factor Notch2 in splenic marginal zone lymphoma.

Splenic marginal zone lymphoma (SMZL) is a lymphoma type of putative marginal zone B-cell origin. No specific genetic alterations have yet been demonstrated in SMZL. Clinically, SMZL is a low-grade B-cell non-Hodgkin lymphoma. However, the presence of p53 mutation, 7q22-7q32 deletion or the absence of somatic hypermutations of immunoglobulin genes has been correlated with a worse prognosis. In this study, we analyzed genome-wide gene expression of 24 cases of SMZL using the microarray technique. The AP-1 transcription factors c-jun, junD, junB, and c-fos as well as Notch2 were found to be specifically up-regulated. These data were confirmed by real-time PCR and immunohistochemical staining of tissue sections. The absence of concordant high expression of the MAP kinases, the signaling cascade leading to AP-1 up-regulation, suggests autoregulation of the AP-1 transcription factors and an important role in SMZL oncogenesis. High expression of Notch2, a transcription factor that induces marginal zone B-cell differentiation, is highly suggestive for a marginal zone B-cell origin of SMZL. In addition, SMZL with the 7q deletion showed high expression of TGF-beta1 and low expression of the DNA helicase XPB, a crucial part of the nucleotide excision repair complex, possibly explaining the more aggressive clinical course of those cases.

Alleles↗
PubMed1988

Nus A protein affects transcriptional pausing and termination in vitro by binding to different sites on the transcription complex.

We examined the in vitro concentration dependence of the effects of Nus A on transcription termination and pausing to determine if Nus A affects both pausing and termination in vitro by binding to a single site on the transcription complex. Nus A was shown to cause maximal increases of pausing at a concentration approximately equimolar to RNA polymerase. However, the effects of Nus A on termination require much higher Nus A concentrations than are required for pausing. It is therefore likely that the effects of Nus A on pausing and termination result from the binding of Nus A to different sites on the transcription complex. Since proteins that probably bind RNA nonspecifically were also shown to strongly reduce termination at a Rho-dependent terminator, Nus A may decrease Rho-dependent termination by binding nonspecifically to RNA. This proposal is consistent with most of the available data on the in vitro effects of Nus A and provides a mechanistic basis for previously unexplained details of Nus A caused decreases in Rho-dependent termination. We further speculate that most or all of the in vivo roles of Nus A may involve the enhancement of pausing.

Bacterial Proteins↗
PubMed2003

Targeting the transcriptional machinery with unique artificial transcriptional activators.

The link between a growing number of human diseases and misregulation of gene expression has spurred intense interest in artificial transcriptional activators that could be used to restore controlled expression of affected genes. To expand the repertoire of activation domains available for the construction of artificial transcriptional regulators, a selection strategy was used to identify two unique activation domain motifs. These activation domains bear little sequence homology to endogenous counterparts and bind to unique sites within the transcriptional machinery. A comparison with two well-characterized activation domains, VP2 and P201, demonstrated for the first time that functional potency is not solely dictated by binding affinity. Finally, the selection strategy described is readily applicable to the identification of small molecule activation domains.

Amino Acid Sequence↗
PubMed2000

Role of inverted DNA repeats in transcriptional and post-transcriptional gene silencing.

Transgenes and endogenous genes are sensitive to silencing, in particular when the genes are tandemly repeated. Their expression can be transcriptionally or post-transcriptionally repressed, or both. It is remarkable that very often, two or more genes or parts of the genes are arranged as inverted repeats (IR). Many of such IRs are dominant silencing loci. They can repress the expression of homologous genes elsewhere in the genome in trans which is usually associated with an increase in the level of DNA methylation. Trans-silencing has been explained by DNA-DNA pairing between a repetitive silencing locus and a homologous target locus. However, there is accumulating evidence that the trans effect might be mediated by dsRNA transcribed from the IR (trans)genes. Besides dsRNA-directed DNA methylation, dsRNA in plants as well as in other systems also induces the degradation of homologous RNAs and silence genes post-transcriptionally. These findings indicate that several features associated with gene silencing can be attributed to the activities of dsRNA, which would explain why inverted transgene repeats are such efficient silencing loci.

Gene Expression Regulation, Plant↗
PubMed2001

Drosophila mitochondrial transcription factor A (d-TFAM) is dispensable for the transcription of mitochondrial DNA in Kc167 cells.

We have cloned cDNA encoding Drosophila mitochondrial (mt) transcription factor A (d-TFAM). RNA interference (RNAi) of d-TFAM by lipofection of haemocyte-derived Kc167 cells with double-stranded RNA reduced d-TFAM to less than 5% of the normal level. Reflecting the ability of TFAM to stabilize mtDNA, RNAi of d-TFAM reduced mtDNA to 40%. Nonetheless, transcription of the ND2 and ND5 genes and their mRNAs remained unchanged for 8 days of the duration of RNAi. We thus show that d-TFAM is not essential for the transcription of Drosophila mtDNA.

Amino Acid Sequence↗