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At least 901 records · Page 50Linked to original sources
PubMed2002

A novel mechanism for the regulation of osteoblast differentiation: transcription of periostin, a member of the fasciclin I family, is regulated by the bHLH transcription factor, twist.

Periostin is a secreted protein that is highly expressed in early osteoblastic cells in vitro and in periosteum and periodontal ligament tissues in vivo. It is known that periostin supports cellular adhesion and spreading in vitro. Although, the mechanisms of transcriptional regulation of periostin are poorly understood, gene-profiling data have revealed that overexpression of Twist, a basic helix-loop-helix (bHLH) transcription factor, resulted in increased periostin expression as validated by Northern blot and reverse transcription-polymerase chain reaction (RT-PCR) analyses. Twist is an important transcription factor for cell type determination and differentiation and has been shown to play an important regulatory role in early osteogenesis. In situ hybridization of mouse calvarial bones indicated that periostin and Twist mRNA are co-localized at the osteogenic fronts of calvarial bones. To characterize the 5' flanking region of the periostin gene, primer extension was carried out to identify the transcription start site, and DNA sequence analysis confirmed the presence of a 'Twist-box' response element. The results of electrophoretic mobility shift assay (EMSA) using nuclear extracts of MC3T3-E1 cells revealed that Twist bound to the Twist-box sequence on the periostin promoter. In vivo footprinting experiments using ligation-mediated PCR (LM-PCR) indicated that the Twist-box sequence was protected in undifferentiated MC3T3-E1 preosteoblasts but not in differentiated MC3T3-E1 osteoblasts. To determine whether Twist actually regulates the periostin expression, 293T cells were transiently co-transfected with the periostin promoter construct and the human Twist expression vector. Reporter analysis indicated that the periostin promoter activities were enhanced by overexpression of Twist. These data suggest that Twist can bind to the periostin promoter in undifferentiated preosteoblasts and up-regulate periostin expression, consistent with the up-regulation of periostin expression by Twist as observed in the gene-profiling data.

5' Flanking Region↗
PubMed1995

Hypoxia-induced transcription of the vascular endothelial growth factor gene is independent of functional AP-1 transcription factor.

In this study, we investigated the functional role of the transcription factor AP-1 in hypoxia-induced expression of the vascular endothelial growth factor (VEGF) by using dexamethasone as an inhibitor of AP-1 activity. Phorbol ester and platelet-derived growth factor (PDGF) cause an increase in VEGF mRNA expression, which is strongly suppressed in the presence of dexamethasone, whereas hypoxia-induced VEGF expression is not inhibited by dexamethasone. Studies using a VEGF promoter luciferase construct show that the phorbol ester and PDGF-induced VEGF expression is mediated at least in part by transcriptional activation of the VEGF promoter, whereas no transcriptional activation is seen under hypoxic conditions. In contrast, hypoxia leads to an increase in VEGF mRNA stability, as confirmed by experiments using actinomycin D as an inhibitor of transcription. These results indicate that hypoxia-induced VEGF expression is independent of AP-1 mediated transcription.

3T3 Cells↗
PubMed1998

Transcription initiation and RNA processing in the mitochondria of the red alga Chondrus crispus: convergence in the evolution of transcription mechanisms in mitochondria.

The mitochondrial DNA (mt DNA) of the red alga Chondrus crispus is shown to be transcribed into two large RNA molecules. These primary transcripts are cleaved once, at the level of a tRNA, then the resulting products are processed via multiple maturation events into either mono- or poly-cistronic RNAs. Transcripts were detected for all genes and open reading frames, except for rps11 and orf172. For both transcription units the initiation of transcription was mapped by in vitro RNA capping and primer extension experiments within inverse repeated sequences at the north pole of the molecule. Consistent with primer extension mapping, putative promoter motifs sharing significant similarities with both chicken and Xenopus mitochondrial promoters were found in the C. crispus mitochondrial genome. Altogether C. crispus mitochondrial DNA appears to be transcribed as animal mtDNA is, suggesting that transcription mechanisms in mitochondria are dependent on the overall organization of the mitochondrial genome irrespective of the eukaryotic phylogeny.

Animals↗
PubMed1992

Transcriptional analysis of the fix ABCXORF1 region of Azorhizobium caulinodans suggests post-transcriptional processing of the fix ABCXORF1 mRNA.

We report here the transcriptional analysis of the fixABCXORF1 region of Azorhizobium caulinodans. This led to the identification of a 0.9 kb transcript covering fixX and ORF1, which was synthesized only under conditions of nitrogen fixation. The 5' end of this transcript was mapped by primer extension and S1 nuclease protection analyses and shown to be located 70 +/- 1 nucleotides upstream of the fixX start codon. By means of transcriptional fixX- and ORF1-lacZ fusions, it was shown that fixX and ORF1 were most probably transcribed from the fixA promoter and that expression of fixX and ORF1 was dependent on NifA activation. This suggests that the 0.9 kb mRNA results from post-transcriptional processing of a large mRNA covering fixA,B,C,X and ORF1. In addition, ORF1 mutants were constructed and were shown not to be impaired in nitrogenase activity.

Base Sequence↗
PubMed1990

Closely spaced and divergent promoters for an aminoacyl-tRNA synthetase gene and a tRNA operon in Escherichia coli. Transcriptional and post-transcriptional regulation of gltX, valU and alaW.

The transcription of the gltX gene encoding the glutamyl-tRNA synthetase and of the adjacent valU and alaW tRNA operons of Escherichia coli K-12 has been studied. The alaW operon containing two tRNA(GGCAla) genes, is 800 base-pairs downstream from the gltX terminator and is transcribed from the same strand. The valU operon, containing three tRNA(UACVal) and one tRNA(UUULys) (the wild-type allele of supN) genes, is adjacent to gltX and is transcribed from the opposite strand. Its only promoter is upstream from the gltX promoters. The gltX gene transcript is monocistronic and its transcription initiates at three promoters, P1, P2 and P3. The transcripts from one or more of these promoters are processed by RNase E to generate two major species of gltX mRNA, which are stable and whose relative abundance varies with growth conditions. The stability of gltX mRNA decreases in an RNase E- strain and its level increases with growth rate about three times more than that of the glutamyl-tRNA synthetase. The 5' region of these mRNAs can adopt a stable secondary structure (close to the ribosome binding site) that is similar to the anticodon and part of the dihydroU stems and loops of tRNA(Glu), and which might be involved in translational regulation of GluRS synthesis. The gltX and valU promoters share the same AT-rich and bent upstream region, whose position coincides with the position of the upstream activating sequences of tRNA and rRNA promoters to which they are similar. This suggests that gltX and valU share transcriptional regulatory mechanisms.

Amino Acyl-tRNA Synthetases↗
PubMed1984

Mutations in Box B of the promoter of a eucaryotic tRNAPro gene affect rate of transcription, processing, and stability of the transcripts.

We have constructed a series of single and double base-pair-substitution mutants in and around the second component (Box B) of the promoter of a tRNAPro gene from C. elegans. Their analysis in in vivo and in vitro transcriptional systems establishes the importance of single nucleotides in the promotion of transcription. Most mutants in the region coding for the TpsiCG stem-loop show a reduced gene expression associated with lack of processing of the primary transcriptional products; in the oocytes these are rapidly degraded, with a half-life considerably shorter than that of wild-type tRNA molecules. In contrast, mutations in the DNA region coding for the anticodon stem-loop do not alter the efficiency of transcription or the processing of the transcripts.

Animals↗
PubMed1990

Selective inhibition of activated but not basal transcription by the acidic activation domain of VP16: evidence for transcriptional adaptors.

The interaction between the chimeric activator GAL4-VP16, consisting of the DNA binding domain of GAL4 and the acidic activation domain of VP16, and its target in the transcriptional machinery was studied in vitro. GAL4-VP16 stimulated transcription from a promoter bearing GAL4 sites, and greatly inhibited transcription from a promoter bearing binding sites for the dA:dT activator and from a basal promoter bearing only a TATA box. Mutations in the acidic domain that reduced activation from the GAL4 site promoter also reduced inhibition from the dA:dT promoter, indicating a similar interaction between VP16 and its target in both processes. Strikingly, if the DNA binding domain of GAL4-VP16 was occupied by a GAL4 site oligonucleotide, the protein inhibited activation by the dA:dT activator but did not inhibit basal transcription. We propose that, under these conditions, GAL4-VP16 acted to titrate an "adaptor" that bridges an interaction between the upstream activator and the basic transcriptional machinery at the TATA box.

Binding Sites↗
PubMed1994

A novel mediator of class II gene transcription with homology to viral immediate-early transcriptional regulators.

Our investigations of mammalian class II gene transcription resulted in identification, purification, and cloning of the corresponding cDNA of a cellular factor (p15) that mediates the effects of several distinct activators on transcription in vitro. Functional deletion analyses revealed a bipartite structure of p15 comprising an amino-terminal regulatory domain and a carboxy-terminal cryptic DNA-binding domain. We provide evidence that activity of p15 is controlled by protein kinases that target the regulatory domain. Structural and functional similarities, including sequence homology to domains essential for cofactor function, cofactor activity, promiscuity with respect to transcriptional activators, and interactions with components of the basal transcription machinery, relate this novel cellular cofactor to viral immediate-early transcriptional regulators.

Amino Acid Sequence↗
PubMed1990

Transcription factors different from the estrogen receptor stimulate in vitro transcription from promoters containing estrogen response elements.

The estrogen response element (ERE) directly linked to a TATA box induces CAT activity in a hormone-dependent manner in Fe 33 cells, the rat hepatoma cell line FTO-2B, stably transfected with the human estrogen receptor (ER). The same promoter construct mediates the stimulation of in vitro transcription. This stimulation is dependent on the presence of the ERE. Induction of transcription in a variety of nuclear extracts derived from mammalian cells is of the same magnitude irrespective of the presence of ER. Similarly, transcription in vitro mediated by B1 vitellogenin 5' flanking sequences in different nuclear extracts is not due to the interaction of the ER with the ERE. Competition analyses with a variety of oligonucleotides reveal that proteins different from the ER, which recognize ERE-like DNA elements, functionally interact with the ERE in vitro. These experiments suggest that ubiquitous proteins related or even identical to the transcription factor USF (MLTF) activate in vitro transcription in an ERE-dependent manner.

Animals↗
PubMed2006

Analysis of transcriptional modulation of the presenilin 1 gene promoter by ZNF237, a candidate binding partner of the Ets transcription factor ERM.

DNA sequences required for the expression of the human presenilin 1 (PS1) gene have been identified between -118 and +178 flanking the major initiation site (+1) mapped in SK-N-SH cells. Several Ets sites are located both upstream as well as downstream from the +1 site, including an Ets motif present at -10 that controls 90% of transcription in SK-N-SH cells. However, in SH-SY5Y cells, transcription initiates further downstream and requires an alternative set of promoter elements including a +90 Ets motif. Ets2, ER81, ERM and Elk1 were identified by yeast one-hybrid selection in a human brain cDNA library using the -10 Ets motif as a bait. We have shown that ERM recognizes specifically Ets motifs on the PS1 promoter located at -10 as well as downstream at +90, +129 and +165 and activates PS1 transcription with promoter fragments whether or not they contain the -10 Ets site. We have now searched for ERM interacting proteins by yeast two-hybrid selection in a human brain cDNA library using the C-terminal 415 amino acid of ERM as a bait. One of the interacting proteins was ZNF237, a member of the MYM gene family. It is widely expressed in different tissues in eukaryotes under several forms derived by alternative splicing, including a large 382 amino acid form containing a single MYM domain, and 2 shorter forms of 208 and 213 amino acids respectively that do not. We show that both the 382 as well as the 208 amino acid forms are expressed in SK-N-SH cells but not in SH-SY5Y cells. Both forms interact with ERM and repress the transcription of PS1 in SH-SY5Y cells. The effect of both C-terminal and N-terminal deletions indicates that the N-terminal 120 amino acid region is required for interaction with ERM in yeast, and furthermore single amino acid mutations show that residues 112 and 114 play an important role. The repression of transcription in SH-SY5Y cells also appears to require the N-terminal potion of ZNF237 and was affected by mutation of the amino acid 112. Data from electrophoretic mobility shift assays indicate that ERM and possibly ZNF237 interact with a fragment of the PS1 promoter.

Carrier Proteins↗
PubMed2006

Transcription of gonadotropin beta subunit genes involves cross-talk between the transcription factors and co-regulators that mediate actions of the regulatory hormones.

The gonadotropins LH and FSH have distinct temporal patterns of expression as a result of differential regulation by hormones such as GnRH, steroids and activin. This specific regulation is due to diverse sets of transcription factors that are recruited to the promoters of these genes, and recruit specific co-activator complexes which function to stabilize interactions with the general transcription factors and RNA polymerase II, and also to induce covalent modifications of the histone tails at these gene loci. As these molecular mechanisms are elucidated, the nature of nuclear cross-talk between the various hormonally induced pathways is becoming evident, revealing both negative and positive effects of interacting transcription factors and co-regulators. This paper will review current knowledge on the transcriptional regulation of gonadotropin beta subunit gene expression in the chromatin setting, and will present new data pertaining to nuclear cross-talk between the various endocrine-induced pathways regulating gonadotropin gene transcription.

Animals↗
PubMed2003

Role of E.coli transcription-repair coupling factor Mfd in Nun-mediated transcription termination.

Phage HK022 Nun protein excludes phage lambda by binding nascent lambda-nut RNA and inducing termination and transcript release. In contrast, in a purified in vitro system, Nun arrests transcription on lambdaDNA templates without dissociation of the transcription elongation complex (TEC). Our evidence indicates that transcription-repair coupling factor (Mfd) frees Nun-arrested RNA polymerase. The activity of Nun is enhanced in an mfd-null mutant, consistent with prolonged association of Nun with the TEC. Furthermore, expression of lambda nut RNA in the mfd mutant titrates Nun, allowing superinfecting lambda to form plaques. Finally, addition of Mfd releases a Nun-arrested transcription complex in vitro.

Bacterial Proteins↗
PubMed1998

The transcription-repair coupling factor CSA is required for efficient repair only during the elongation stages of RNA polymerase II transcription.

The known nucleotide excision repair (NER) defects of xeroderma pigmentosum (XP) and Cockayne syndrome (CS) cells can be exploited to analyze mechanisms of repair of UV-induced cyclobutane pyrimidine dimers (CPDs) at nucleotide (nt.) resolution. The two gene products of the CS complementation groups (CSA and CSB) have been implicated in the preferential repair of the transcribed strand of human genes. We had previously described very efficient repair of CPDs at sequences near the transcription initiation site of the human JUN gene in normal fibroblasts. Here, we have analyzed repair in a CSA fibroblast strain. CSA cells exhibited rapid repair near the transcription initiation site (positions -45 to +15) but were deficient in repair of sequences on the transcribed strand beginning around nt. +20. There was also no strand-selective repair of sequences further downstream of the start site (+260 to +450). The results suggest that the transcription-repair coupling factor (TRCF) CSA is required for efficient repair only during the elongation stages of RNA polymerase II transcription. We also discuss possible mechanisms of differential repair observed near the transcription initiation site in XP and CS cells and conclude that these in vivo repair data support some recent models obtained from nucleotide excision repair experiments in vitro.

Cell Line↗
PubMed1998

Ca2+ influx regulates BDNF transcription by a CREB family transcription factor-dependent mechanism.

CREB is a transcription factor implicated in the control of adaptive neuronal responses. Although one function of CREB in neurons is believed to be the regulation of genes whose products control synaptic function, the targets of CREB that mediate synaptic function have not yet been identified. This report describes experiments demonstrating that CREB or a closely related protein mediates Ca2+-dependent regulation of BDNF, a neurotrophin that modulates synaptic activity. In cortical neurons, Ca2+ influx triggers phosphorylation of CREB, which by binding to a critical Ca2+ response element (CRE) within the BDNF gene activates BDNF transcription. Mutation of the BDNF CRE or an adjacent novel regulatory element as well as a blockade of CREB function resulted in a dramatic loss of BDNF transcription. These findings suggest that a CREB family member acts cooperatively with an additional transcription factor(s) to regulate BDNF transcription. We conclude that the BDNF gene is a CREB family target whose protein product functions at synapses to control adaptive neuronal responses.

Animals↗
PubMed2002

A regulating element essential for PDGFRA transcription is recognized by neural tube defect-associated PRX homeobox transcription factors.

We have previously shown that deregulated expression of the platelet-derived growth factor alpha-receptor (PDGFRA) can be associated with neural tube defects (NTDs) in both men and mice. In the present study, we have investigated the transcription factors that control the up-regulation of PDGFRA expression during differentiation of early embryonic human cells in culture. In Tera-2 embryonal carcinoma cells, PDGFRA expression is strongly enhanced upon differentiation induced by retinoic acid and cAMP treatment. Here we show that the corresponding increase in promoter activity is controlled by an ATTA-sequence-containing element located near the transcription initiation site, which is bound by a transcriptional complex that includes PBX and PRX homeobox transcription factors. Mutation of the putative binding sites for these transcription factors results in strong impairment of PDGFRA promoter activity in differentiated cells. Since functional inactivation of Prx genes has been associated with NTDs in mice, these data support a model in which improper PDGFRA expression as a result of mutations in or altered binding of its upstream regulators may be causally related to NTDs.

Amino Acid Sequence↗
PubMed2005

RFP represses transcriptional activation by bHLH transcription factors.

Basic helix-loop-helix (bHLH) transcription factors play a pivotal role in the regulation of tumorigenesis, and also in a wide range of other developmental processes in diverse species from yeast to humans. Here we demonstrate for the first time that Ret finger protein (RFP), a member of the TRIM family of proteins initially identified as a recombined transforming gene from a human lymphoma, is a novel interaction partner for four different bHLH proteins (SCL, E47, MyoD and mASH-1), but does not interact with GATA-1 or PU.1. Interaction with SCL required the B-box and first coiled-coil region of RFP together with the bHLH domain of SCL. RFP was able to repress transcriptional activation by E47, MyoD and mASH-1, but not by members of several other transcription factor families. Transcriptional repression by RFP was trichostatin A sensitive and did not involve an Id-like mechanism or ubiquitination with subsequent degradation of bHLH proteins. Instead, our results suggest that bHLH transcription factors are regulated by a previously undescribed interaction with RFP, which functions to recruit HDAC and/or Polycomb proteins and thus repress target genes of bHLH proteins. These results reveal an unexpected link between the bHLH and TRIM protein families.

Animals↗
PubMed2005

Transcriptional and post-transcriptional gene regulation of HTLV-1.

Adult T-cell leukemia (ATL) is an aggressive hematologic malignancy caused by human T-cell leukemia virus type I (HTLV-1). Tax, encoded by the HTLV-1 pX region, has been recognized by its pleiotropic actions to play a critical role in leukemogenesis. Three highly conserved 21-bp repeat elements located within the long terminal repeat, commonly referred to as Tax-responsive element 1 (TRE-1), are critical to Tax-mediated viral transcriptional activation through complex interaction with cyclic AMP-responsive element binding protein (CREB), CBP/p300 and PCAF. Tax has also been shown to activate transcription from a number of critical cellular genes through the NF-kappaB and serum-responsive factor pathways. Tax transactivation has been attributed to the protein's interaction with transcription factors, chromatin remodeling complexes, cell cycle and repair genes. In this review, we will discuss some of the latest findings on this fascinating viral activator and highlight its regulation of cellular factors including CREB, p300/CBP and their effect on RNA polymerase II and chromatin remodeling, as well as its role in cytoplasmic and nuclear function. We will highlight the possible contribution of each factor, discuss Tax's critical peptide domains and highlight its post-transcriptional modifications. It is quite obvious that, collectively, Tax's effects on a wide variety of cellular targets cooperate in promoting cell proliferation and leukemogenesis. In addition, the post-transcriptional effects of Rex play an important role in virus replication. Understanding these interactions at a molecular level will facilitate the targeted development of drugs to effectively inhibit or treat ATL.

Gene Expression Regulation, Viral↗
PubMed2001

Characterization of the interaction between the transcription factors human polyamine modulated factor (PMF-1) and NF-E2-related factor 2 (Nrf-2) in the transcriptional regulation of the spermidine/spermine N1-acetyltransferase (SSAT) gene.

Polyamines and polyamine analogues have been demonstrated to modulate the transcription of various genes. Spermidine/spermine N(1)-acetyltransferase (SSAT) is transcriptionally regulated through the interaction of at least two trans-acting transcription factors, NF-E2-related factor 2 (Nrf-2) and PMF-1 (polyamine modulated factor-1). Nrf-2 has previously been shown to regulate transcription of other genes through interactions between its C-terminal leucine zipper and the leucine-zipper region of other members of the small Maf protein family (the term "Maf" is derived from MusculoAponeurotic-Fibrosarcoma virus). Here it is demonstrated that the interaction between Nrf-2 and PMF-1 is mediated through the binding of the leucine-zipper region of Nrf-2 and a C-terminal coiled-coil region of PMF-1 that does not contain a leucine zipper. Mutations that interrupt either the leucine zipper of Nrf-2 or the coiled-coil region of PMF-1 are demonstrated to alter the ability of these factors to interact, thus their ability to regulate the transcription of the SSAT gene is lost.

Acetyltransferases↗