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At least 235 records · Page 13Linked to original sources
PubMed1995

Repression of vertebrate RNA polymerase III transcription by DNA binding proteins located upstream from the transcription start site.

Derivatives of yeast tRNA and Xenopus tRNA and 5 S RNA genes have been constructed in which natural 5' flanking sequences have been replaced by the binding sites for either the yeast transcription activator protein GCN4 or the three amino-terminal zinc fingers of the Xenopus factor TFIIA (zf1-3). The binding sites for these proteins have been placed at various distances upstream from the start site for transcription initiation in the parent genes. Each of these plasmid DNAs is actively transcribed in both an unfractionated transcription extract prepared from unfertilized Xenopus eggs and in a reconstituted Xenopus transcription system. Binding of the test proteins to plasmid DNAs harboring the cognate binding sites severely represses transcription when these binding sites are located less than approximately 40 base-pairs upstream from the transcription start site. The DNA-binding proteins are without effect on the transcription of plasmids lacking binding sites or when the binding sites are located further upstream. Assembly of DNA templates into a complete transcription complex prior to addition of the DNA-binding proteins prevents repression. Proteins present in a fraction containing TFIIIB are necessary for this reversal of repression. These data suggest that vertebrate TFIIIB binds upstream from class III genes and this binding can be prevented by occlusion of the TFIIIB binding site by the test proteins GCN4 and zf1-3.

Animals↗
PubMed1998

hTFIIIB-beta stably binds to pol II promoters and recruits RNA polymerase III in a hTFIIIC1 dependent way.

It has been shown that under specific conditions, transcription of protein coding genes can be efficiently initiated by RNA polymerase (pol) III in vitro. We examined the formation and composition of such pol III transcription complexes on the duck histone H5 and alphaA-globin promoters and found that the essential step for the formation of pol III transcription complexes on these pol II promoters was the stable binding of transcription factor (TF) IIIB-beta. For this process, the intact TFIIIB-beta complex, consisting of TBP and associated factors (TAFs) was needed and the prior association of pol III assembly factors was not necessary. We demonstrate for the first time that hTFIIIB-beta alone is able to bind to pol II promoter DNA. This resulted in a very stable complex which was resistant to high concentrations of heparin. Although immunodepletion revealed that TBP is essentially required for complex formation, other components of hTFIIIB-beta must also be involved, since TBP itself is unable to form heparin-resistant complexes and does not mediate pol III commitment per se. pol III is recruited to these pol II promoters in a strictly TFIIIC1 dependent way. After binding of TFIIIB-beta, the addition of TFIIIC1 and pol III were sufficient to yield productive pol III transcription complexes, which utilized the correct pol II initiation site. From these findings, we postulate that TFIIIC1 is involved in the recruitment of pol III and may thus form a bridge between TFIIIB-beta and the enzyme. This finding provides the first evidence for functional contacts between TFIIIC1 and pol III, which could be of general importance for the assembly of pol III transcription complexes.

Chromatography, Liquid↗
PubMed1993

Studies on class III gene transcription.

In an attempt to understand the functional role of individual transcription factors, we have carried out S1 nuclease analyses of in vitro synthesized RNA using partially purified HeLa cell factors and truncated 5S and tDNA. The results indicate that faithful initiation of 5S gene transcription depends on the presence of IIIA, IIIB and IIIC in addition to RNA polymerase III. On the other hand, tDNA transcription initiation requires IIIB and IIIC and RNA polymerase III. In addition, we found that either 'A' block promoter or 'B' block alone can not serve as a template for the initiation of tDNA transcription. When an ultraviolet irradiated 5S DNA was used as a template, transcription is minimally affected at a lower dose suggesting that small differences in the helical structure may not have much effect on the transcription machinery. These results along with an in vitro attempt to reproduce Xenopus 5S RNA gene regulation are presented.

Animals↗
PubMed2001

Mammalian histone acetyltransferases and their complexes.

One of the key questions in the current molecular genetics of eukaryotes is how genetic information is retrieved from tightly packed chromatin. Acetylation of core histone N-termini is implicated in the regulation of chromatin function, and I summarize what is known about the mammalian enzymes that promote this posttranslational histone modification. Chromatin is important in gene expression not only because of the accessibility problem that it poses for the transcriptional machinery but also with regard to the phenomenon of chromatin memory, i.e. the ability of alternative chromatin states to be maintained through many cell divisions. This phenomenon is believed to be central to epigenetic inheritance, an important concept in developmental biology, which is also emerging as a contributing factor in cancer and other health disorders. Analyses of the composition of large multiprotein acetyltransferase complexes suggest their role in the mechanisms of epigenetic inheritance. The review will discuss some models pertinent to this function of histone acetyltransferases.

Acetyltransferases↗
PubMed1989

Transcription of 5S RNA genes containing insertion mutation and the assembly of preinitiation complexes.

The transcription of Xenopus 5S RNA genes containing insertions in and around the intragenic control region has been analyzed in a HeLa cell-free system. A 15 bp insertion within the intragenic region greatly diminished binding of TFIIIA and concomitantly reduced binding of TFIIIB and transcription in vitro. This study helps to define more precisely the promoter organization of Xenopus 5S RNA genes for the efficient interactions with transcription factors.

Animals↗
PubMed1990

DNA methylation inhibits transcription by RNA polymerase III of a tRNA gene, but not of a 5S rRNA gene.

Methylation of cytosine in the DNA inhibits the transcription by RNA polymerase II in higher eukaryotes, but has no influence on RNA polymerase I transcription. The effect on RNA polymerase III was unknown, so far. Two polymerase III genes: a type 1 5S rRNA gene and a type 2 tRNA gene were methylated in vitro with a purified eukaryotic DNA methyltransferase (EC2.1.1.37) and their transcription was analyzed in Xenopus oocytes. The 5S rRNA gene, an oocyte 5S rRNA gene from X. laevis which is subject to developmental inactivation, was not affected by methylation. Conversely, transcription of the tRNA gene was 80% inhibited by methylation with the eukaryotic methyltransferase. HhaI and HpaII methylation left its transcription unaffected.

Animals↗
PubMed1996

A human B-box-binding protein downregulated in adenovirus 5-transformed human cells.

Internal promoters of some genes transcribed by RNA polymerase III (e.g. tRNA genes, adenovirus VA1 RNA gene, human retroposons of the Alu family) contain a conserved sequence element, B-box, interacting with basal transcription factor TFIIIC2 which initiates assembly of the full transcription complex on the genes, and which represents the major determinant of the efficiency of their expression. In this study we have identified in human nuclear extracts a protein which interacts with VA1 B-box DNA and forms a high-affinity complex which is very stable after the addition of a large excess of competitor DNA. Unlike TFIIIC2, the B-box-binding activity of the B-box-binding protein is found to be decreased in adenovirus 5-transformed human cells. In these cells (line 293) increased transcription of VA1 and tRNA genes in vivo and in vitro was previously detected by other workers. Our results suggest that besides TFIIIC2, an additional B-box-binding protein factor may be involved in the regulation of expression of the RNA polymerase III-transcribed genes.

Adenoviruses, Human↗
PubMed1988

Interaction of tRNA transcription factors with satellite I DNA from Xenopus laevis.

A cloned repeat of Xenopus laevis satellite I DNA was tested for the ability to form stable complexes with tRNA transcription factors in vitro. In template exclusion studies, the satellite I DNA competed efficiently with a tRNA gene for binding of yeast RNA polymerase III transcription factors. DNase I footprinting further showed that transcription factor TF IIIC alone bound to satellite I DNA at both the A block and B block consensus promoter sequences immediately downstream from the transcription start point. The strength and position of these associations indicate that satellite I DNA is a potential site for association of the same DNA-binding proteins that activate tRNA gene transcription.

Animals↗
PubMed1991

The assembly of functional preinitiation complexes and transcription of 5S RNA-encoding genes containing point mutations.

The transcription of several Syrian hamster 5S RNA-encoding genes (5S genes) containing single and multiple point mutations in and around the intragenic control region has been analyzed in a HeLa cell-free system. Although most genes with point mutations displayed normal levels of transcription, several exhibited a three- to fivefold reduction in transcription. These mutations interfere with the interaction between the 5S genes and the soluble factors. The above studies help to establish the importance of specific nucleotides within the 5S gene for productive interactions of individual transcription factors in vitro.

Animals↗
PubMed1996

Facilitated recycling pathway for RNA polymerase III.

We show that the high in vitro transcription efficiency of yeast RNA pol III is mainly due to rapid recycling. Kinetic analysis shows that RNA polymerase recycling on preassembled tDNA.TFIIIC.TFIIIB complexes is much faster than the initial transcription cycle. High efficiency of RNA pol III recycling is favored at high UTP concentrations and requires termination at the natural termination signal. Runoff transcription does not allow efficient recycling. The reinitiation process shows increased resistance to heparin as compared with the primary initiation cycle, as if RNA polymerase was not released after termination. Indeed, template competition assays show that RNA pol III is committed to reinitiate on the same gene. A model is proposed where the polymerase molecule is directly transferred from the termination site to the promoter.

DNA, Fungal↗
PubMed2001

Genes for human general transcription initiation factors TFIIIB, TFIIIB-associated proteins, TFIIIC2 and PTF/SNAPC: functional and positional candidates for tumour predisposition or inherited genetic diseases?

TFIIIB, TFIIIC2, and PTF/SNAPC are heteromultimeric general transcription factors (GTFs) needed for expression of genes encoding small cytoplasmic (scRNAs) and small nuclear RNAs (snRNAs). Their activity is stimulated by viral oncogenes, such as SV40 large T antigen and Adenovirus E1A, and is repressed by specific transcription factors (STFs) acting as anti-oncogenes, such as p53 and pRb. GTFs role as final targets of critical signal transduction pathways, that control cell proliferation and differentiation, and their involvement in gene expression regulation suggest that the genes encoding them are potential proto-oncogenes or anti-oncogenes or may be otherwise involved in the pathogenesis of inherited genetic diseases. To test our hypothesis through the positional candidate gene approach, we have determined the physical localization in the human genome of the 11 genes, encoding the subunits of these GTFs, and of three genes for proteins associated with TFIIIB (GTF3BAPs). Our data, obtained by chromosomal in situ hybridization, radiation hybrids and somatic cell hybrids analysis, demonstrate that these genes are present in the human genome as single copy sequences and that some cluster to the same cytogenetic band, alone or in combination with class II GTFs. Intriguingly, some of them are localized within chromosomal regions where recurrent, cytogenetically detectable mutations are seen in specific neoplasias, such as neuroblastoma, uterine leyomioma, mucoepidermoid carcinoma of the salivary glands and hemangiopericytoma, or where mutations causing inherited genetic diseases map, such as Peutz-Jeghers syndrome. Their molecular function and genomic position make these GTF genes interesting candidates for causal involvement in oncogenesis or in the pathogenesis of inherited genetic diseases.

Chromosome Mapping↗
PubMed2004

Mitogenic stimulation of transcription by RNA polymerase III.

Regulation of protein synthesis is an important aspect of growth control. RNA polymerase (pol) III plays a key role in this process by catalysing production of tRNA and 5 S rRNA. Growth factors trigger a rapid increase in pol III activity and this is essential for cell proliferation. The transcription factor TFIIIB plays a key role in controlling pol III activity and is a target for regulation by a number of mechanisms. This review will focus on how TFIIIB is targeted by these proteins in response to mitogen stimulation.

Animals↗
PubMed2006

Transcription factor TFIIIB and transcription by RNA polymerase III.

pol (RNA polymerase) III is charged with the task of transcribing nuclear genes encoding diverse small structural and catalytic RNAs. We present a brief review of the current understanding of several aspects of the pol III transcription apparatus. The focus is on yeast and, more specifically, on Saccharomyces cerevisiae; preponderant attention is given to the TFs (transcription initiation factors) and especially to TFIIIB, which is the core pol III initiation factor by virtue of its role in recruiting pol III to the transcriptional start site and its essential roles in forming the transcription-ready open promoter complex. Certain relatively recent developments are also selected for brief comment: (i) the genome-wide analysis of occupancy of pol III-transcribed genes (and other loci) by the transcription apparatus and the location of pol III transcription in the cell; (ii) progress toward a mechanistic and molecular understanding of the regulation of transcription by pol III in yeast; and (iii) recent experiments identifying a high mobility group protein as a fidelity factor that assures selection of the precise transcriptional start site at certain pol III promoters.

Gene Expression Regulation↗
PubMed2000

RNA polymerase III transcription factor TFIIIC2 is overexpressed in ovarian tumors.

Most transformed cells display abnormally high levels of RNA polymerase (pol) III transcripts. Although the full significance of this is unclear, it may be fundamental because healthy cells use two key tumor suppressors to restrain pol III activity. We present the first evidence that a pol III transcription factor is overexpressed in tumors. This factor, TFIIIC2, is a histone acetyltransferase that is required for synthesis of most pol III products, including tRNA and 5S rRNA. TFIIIC2 is a complex of five polypeptides, and mRNAs encoding each of these subunits are overexpressed in human ovarian carcinomas; this may explain the elevated TFIIIC2 activity that is found consistently in the tumors. Deregulation in these cancers is unlikely to be a secondary response to rapid proliferation, because there is little or no change in TFIIIC2 mRNA levels when actively cycling cells are compared with growth-arrested cells in culture. Using purified factors, we show that raising the level of TFIIIC2 is sufficient to stimulate pol III transcription in ovarian cell extracts. The data suggest that overexpression of TFIIIC2 contributes to the abnormal abundance of pol III transcripts in ovarian tumors.

Acetyltransferases↗