Search

The ceplR genes encode an N-acyl homoserine lactone (AHL)-dependent quorum-sensing system consisting of an AHL synthase that directs the synthesis of N-octanoyI-L-homoserine lactone (OHL) and N-hexanoyI-L-homoserine lactone and a transcriptional regulator. The virulence of cepIR mutants was examined in two animal models. Rats were infected with agar beads containing Burkholderia cenocepacia K56-2, K56-12 (cepl: :[Tp.sup.r]) or K56-R2 (cepR'' Tn5-OT182). At 10 days post-infection, the extent of lung histopathological changes was significantly lower in lungs infected with K56-12 or K56-R2 compared to the parent strain. Intranasal infections were performed in [Cftr.sup.(-/-)] mice and their wild-type siblings. K56-2 was more virulent in both groups of mice. K56-12 was the least virulent strain and was not invasive in the [Cftr.sup.(-/-)] mice. OHL was readily detected in lung homogenates from [Cftr.sup.(-/-)] mice infected with K56-2 but was only detected at levels slightly above background in a few mice infected with K56-12. Lung homogenates from mice infected with K56-2 had significantly higher levels of the inflammatory mediators murine macrophage inflammatory protein-2, KC/N51, interleukin-1 [beta] and interleukin-6 than those from K56-12-infected animals. These studies indicate that a functional CepIR quorum-sensing system contributes to the severity of B. cenocepacia infections. A zinc metalloprotease gene (zmpA) was shown to be regulated by CepR and may be one of the factors that accounts for the difference in virulence between the cepl mutant and the parent strain.

The first committed step in the purine de novo synthesis pathway is performed by amidophosphoribosyl-transferase (EC 2.4.2.14) or Prat. Drosophila melanogaster Prat is an essential gene with a promoter that lacks a TATA-box and initiator element and has multiple transcription start sites with a predominant start site. To study the regulation of Prat expression in the adult eye, we used the Prat:bw reporter gene, in which the Prat coding region was replaced with the brown (bw) coding region. The pale-orange eye color of a single copy of Prat:bw prompted us to use a multicopy array of Prat:bw that was derived using P transposase mutagenesis and produces a darker-orange eye color in a [bw.sup.D]; st genetic background. We used a 13-copy array of Prat:bw as a tool to recover dominant EMS-induced mutations that affect the expression of the transgene. After screening 21,000 [F.sub.1]s for deviation from the orange eye color, we isolated 23 dominant modifiers: 21 suppressors (1 Y-linked, 5 X-linked, 4 2-linked, and 11 3-linked) and 2 enhancers (1 2-linked and 1 3-linked). Quantification of their effect on endogenous Prat gene expression, using RT-PCR in young adult fly heads, identifies a subset of modifiers that are candidates for genes involved in regulating Prat expression.

The transcriptomes of vancomycin intermediate-resistance Staphylococcus aureus (VISA) clinical isolates HIP5827 and Mu50 (MIC = 8 [micro]g/ml) were compared to those of highly vancomycin-resistant S. aureus (VRSA; MIC = 32 [micro]/ml) passage derivatives by microarray. There were 35 genes with increased transcription and 16 genes with decreased transcription in common between the two VRSAs compared to those of their VISA parents. Of the 35 genes with increased transcription, 15 involved purine biosynthesis or transport, and the regulator (purR) of the major purine biosynthetic operon (purE-purD) was mutant. We hypothesize that increased energy (ATP) is required to generate the thicker cell walls that characterize resistant mutants.

CsrA is a global regulator that binds to two sites in the glgCAP leader transcript, thereby blocking ribosome access to the glgC Shine-Dalgarno sequence. The upstream CsrA binding site (GCACACGGAU) was used to search the Escherichia coli genomic sequence for other genes that might be regulated by CsrA. cstA contained an exact match that overlapped its Shine-Dalgarno sequence, cstA was previously shown to be induced by carbon starvation and to encode a peptide transporter. Expression of a cstA'-'lacZ translational fusion in wild-type and csrA mutant strains was examined. Expression levels in the csrA mutant were approximately twofold higher when cells were grown in Luria broth (LB) and 5- to 10-fold higher when LB was supplemented with glucose. It was previously shown that cstA is regulated by the cyclic AMP (cAMP)-cAMP receptor protein complex and transcribed by E[sigma.sup.70] We investigated the influence of [[sigma].sup.S] on cstA expression and found that a [[sigma].sup.S] deficiency resulted in a threefold increase in cstA expression in wild-type and csrA mutant strains; however, CsrA-dependent regulation was retained. The mechanism of CsrA-mediated cstA regulation was also examined in vitro. Cross-linking studies demonstrated that CsrA is a homodimer. Gel mobility shift results showed that CsrA binds specifically to cstA RNA, while coupled-transcription-translation and toeprint studies demonstrated that CsrA regulates CstA synthesis by inhibiting ribosome binding to cstA transcripts. RNA footprint and boundary analyses revealed three or four CsrA binding sites, one of which overlaps the cstA Shine-Dalgarno sequence, as predicted. These results establish that CsrA regulates translation of cstA by sterically interfering with ribosome binding.

A variety of environmental and metabolic cues trigger the transient activation of the alternative transcription factor SigB of Bacillus subtilis, which subsequently leads to the induction of more than 150 general stress genes. This general stress regulon provides nongrowing and nonsporulated cells with a multiple, nonspecific, and preemptive stress resistance. By a proteome approach we have detected the expression of the SigB regulon during continuous growth at low temperature (15[degrees]C). Using a combination of Western blot analysis and SigB-dependent reporter gene fusions, we provide evidence for high-level and persistent induction of the sigB operon and the SigB regulon, respectively, in cells continuously exposed to low temperatures. In contrast to all SigB-activating stimuli described thus far, induction by low temperatures does not depend on the positive regulatory protein RsbV or its regulatory phosphatases RsbU and RsbP, indicating the presence of an entirely new pathway for the activation of SigB by chill stress in B. subtilis. The physiological importance of the induction of the general stress response for the adaptation of B. subtilis to low temperatures is emphasized by the observation that growth of a sigB mutant is drastically impaired at 15[degrees]C. Inclusion of the compatible solute glycine betaine in the growth medium not only improved the growth of the wild-type strain but rescued the growth defect of the sigB mutant, indicating that the induction of the general stress regulon and the accumulation of glycine betaine are independent means by which B. subtilis cells cope with chill stress.

Secondary RNA polymerase sigma factors in many bacteria are responsible for regulating a vast range of processes including virulence. A protein ([[sigma].sup.x]) in the gram-positive human pathogen Streptococcus pyogenes (the group A Streptococcus or GAS) was recently shown to function in vitro as a secondary sigma factor. We report here the isolation of a mutant in which both sigX genes are inactivated, show that [[sigma].sup.x] functions in GAS cells, and show that the amount of [[sigma].sup.x] is controlled at two levels. Primer extension analysis indicates that sigX transcription is low in GAS cells grown in Todd-Hewitt yeast broth, and immunoblot assays with a [[sigma].sup.x]-specific polyclonal antibody demonstrate that the protein does not accumulate in these cells. To increase the level of sigX transcription in GAS, we constructed a strain that constitutively expresses the sigX gene from a heterologous promoter. Expression of sigX from this promoter led to transcription of the [[sigma].sup.x]-dependent cinA promoter in GAS cells. We found that expression of the sigX gene in a clpP mutant strain resulted in greater accumulation of [[sigma].sup.x] protein, which resulted in higher levels of transcription from the [[sigma].sup.x]-dependent promoters cinA, smf, and cglA. In addition, a clpP mutant containing sigX only at its wild-type loci on the chromosome generated more transcription from the [[sigma].sup.x]-dependent cinA promoter than did the wild-type parental strain. Therefore, [[sigma].sup.x] activity in GAS is limited by low-level transcription of the sigX structural genes and by clpP, which appears to negatively regulate [[sigma].sup.x] accumulation.

Transcription of the Escherichia coli osmC gene is induced by several stress conditions, osmC is expressed from two overlapping promoters, osmCpl and osmCp2. The proximal promoter, osmCp2, is transcribed at the entry into the stationary phase by the [[sigma].sup.s] sigma factor. The distal promoter, osmCpl, is activated by NhaR and RcsB. NhaR is a positive regulator of the LysR family and is known to be an activator of the nhaA gene encoding an [Na.sup.+]/[H.sup.+] antiporter. RcsB is the response regulator of the RcsCDB His-Asp phosphorelay signal transduction system. Genetic data indicated that activation of osmCpl by both NhaR and RcsB requires the same short sequences upstream of the--35 region of the promoter. Accordingly, DNase I footprint analysis indicated that both activators protect an overlapping region close to the--35 box of the promoter and suggested that the regulatory effect is direct. Despite the overlap of the binding sites, each activator acts independent of the other and is specific for a particular stress. NhaR can stimulate osmCpl in response to an osmotic signal even in the absence of RcsB. RcsB is responsible for the induction of osmCpl by alteration of the cell envelope, even in the absence of NhaR. osmCpl as an example of multiple-stress-responsive promoter is discussed in light of a comparison of the NhaR and RcsB target regions in the Enterobacteriaceae.

The SlyA protein of Salmonella enterica serovar Typhimuriuim is a member of the MarR family of transcription regulators and is required for virulence and survival in professional macrophages. Isolated SlyA protein was able to bind a specific DNA target without posttranslational modification. This suggested that SlyA might not be activated by directly sensing an external signal but rather that the intracellular concentration of SlyA is enhanced in appropriate environments through the action of other transcription factors. Analysis of slyA transcription reveals the presence of a promoter region located upstream of the previously recognized SlyA repressed promoter. The newly identified upstream promoter region did not respond to SlyA but was activated by Mg(II) starvation in a PhoP-dependent manner. We present here evidence for a direct link between two transcription factors (PhoP and SlyA) crucial for Salmonella virulence.

Bacteriophage PM2 is the only described member of the Corticoviridae family. It is an icosahedral dsDNA virus with a membrane residing underneath the protein coat. PM2 infects some gram-negative Pseudoalteromonas spp. In the present study, we mapped the viral promoters and showed that the PM2 genome consists of three operons. Four new virus genes were assigned based on their function in transcription. Proteins P15 and P16 are shown to repress early transcription, and proteins P13 and P14 are shown to activate late transcription events. The early regulatory region, containing genes for proteins P15 and P16, as well as the newly identified early promoter region in PM2, has significant sequence similarity with the Pseudoalteromonas pAS28 plasmid. P14, the transcription activator for the structural genes, has a zinc finger motif homologous to archaeal and eukaryotic TFIIS-type regulatory factors.

The transcription factor absent, small, or homeotic discs 2 (ash2) gene is a member of the trithorax group of positive regulators of homeotic genes. Mutant alleles for ash2 are larval/pupal lethals and display imaginal disc and brain abnormalities. The allele used in this study is a true mutant for the trithorax function and lacks the longest transcript present in wild-type flies. In an attempt to identify gene targets of ash2, we have performed an expression analysis by using cDNA microarrays. Genes involved in cell cycle, cell proliferation, and cell adhesion are among these targets, and some of them are validated by functional and expression studies. Even though trithorax proteins act by modulating chromatin structure at particular chromosomal locations, evidence of physical aggregation of ash2-regulated genes has not been found. This work represents the first microarray analysis, to our knowledge, of a trithorax-group gene.

Insig-1 and -2 are closely related proteins of the endoplasmic reticulum (ER) that block proteolytic activation of sterol regulatory element-binding proteins (SREBPs), transcription factors that activate the synthesis of cholesterol and fatty acids in liver and other organs. When cellular cholesterol levels are high, Insig proteins bind and trap SREBP cleavage-activating protein (SCAP), retaining it in the ER and preventing it from escorting SREBPs from ER to the site of proteolytic activation in the Golgi complex. Here, we report the discovery of a liver-specific transcript of Insig-2, designated Insig-2a. This transcript and the ubiquitous transcript, designated Insig-2b, differ through the use of different promoters that produce different noncoding first exons that splice into a common second exon. Although the Insig-2a and -2b mRNAs encode identical proteins, they differ in patterns of regulation. Insig-2a is the predominant transcript in livers of fed animals, and it is selectively down-regulated by insulin. Insig-2a mRNA increases when mice are fasted, and it declines when they are refed. The transcript also increases in livers of rats whose insulin-secreting pancreatic beta cells have been destroyed by streptozotocin, and it is reduced when insulin is injected. The insulin-mediated fall in Insig-2a may allow SREBP-1c to be processed, thereby allowing insulin to stimulate fatty acid synthesis, even under conditions in which hepatic cholesterol levels are elevated.

Modulation of the structure of a leader RNA to control formation of an intrinsic termination signal is a common mechanism for regulation of gene expression in bacteria. Expression of the S box genes in Gram-positive organisms is induced in response to limitation for methionine. We previously postulated that methionine availability is monitored by binding of a regulatory factor to the leader RNA and suggested that methionine or S-adenosylmethionine (SAM) could serve as the metabolic signal. In this study, we show that efficient termination of the S box leader region by bacterial RNA polymerase depends on SAM but not on methionine or other related compounds. We also show that SAM directly binds to and induces a conformational change in the leader RNA. Both binding of SAM and SAM-directed transcription termination were blocked by leader mutations that cause constitutive expression in vivo. Overproduction of SAM synthetase in Bacillus subtilis resulted in delay in induction of S box gene expression in response to methionine starvation, consistent with the hypothesis that SAM is the molecular effector in vivo. These results indicate that SAM concentration is sensed directly by the nascent transcript in the absence of a trans-acting factor.

The Foxl1 gene, which encodes a winged helix transcriptional regulator, is expressed in the mesenchymal layer of developing and mature gastrointestinal tract. Foxl1-deficient mice exhibit various defects not only in the epithelial layer of the gastrointestinal tract but also in gut-associated lymphoid tissues. In the small intestine of Foxl1-deficient mice, the formation of Peyer's patches is affected, particularly in the caudal region. This alteration is shown to be due to the delayed formation of Peyer's patches organizing centers as revealed by the expressions of VCAM1 and IL-7 receptor [alpha]-chain at 17.5 days postcoitus. Peyer's patch defects are concordant with the significantly decreased expression of Lymphotoxin [beta]-receptor in the caudal region of fetal intestine. Foxl1 is suggested to regulate the responsiveness of fetal intestinal mesenchymal cells to inductive signals mediated by Lymphotoxins during Peyer's patch organogenesis. In addition, constitutive outgrowth of colonic patches due to defects in radioresistant stromal components of colonic patches are seen in Foxl1-deficient mice. Because of the functional similarities of hypertrophic colonic patches to those seen in hapten-induced experimental colitis, this hypertrophy is suggested to involve Lymphotoxin [beta]-receptor signaling. Together, the data suggest that Foxl1 might be involved in cellular responses of gut-associated lymphoid tissues dependent upon the Lymphotoxins/Lymphotoxin [beta]-receptor axis. Keywords: Foxl1; Peyer's patch; Colonic patch; Gut mesenchyme; Lymphotoxins; Mouse

DNA sequences containing short adenine tracts are intrinsically curved and play a role in transcriptional regulation. Despite many high-resolution NMR and x-ray studies, the origins of curvature remain disputed. Long-range restraints provided by 85 residual dipolar couplings were measured for a DNA decamer containing an adenine [(A).sub.4]-tract and used to refine the structure. The overall bend in the molecule is a result of in-phase negative roll in the A-tract and positive roll at its 5' junction, as well as positive and negative tilt inside the A-tract and near its junctions. The bend magnitude and direction obtained from NMR structures is 9.0[degrees] into the minor groove in a coordinate frame located at the third AT base pair. We evaluated long-range and wedge models for DNA curvature and concluded that our data for A-tract curvature are best explained by a 'delocalized bend' model. The global bend magnitude and direction of the NMR structure are in excellent agreement with the junction model parameters used to rationalize gel electrophoretic data and with preliminary results of a cyclization kinetics assay from our laboratory.

The C-terminal domain (CTD) of the largest subunit of RNA polymerase II (RNAPII) is heavily phosphorylated during the transition from transcription initiation to the establishment of an elongation-competent transcription complex. FCP1 is the only phosphatase known to be specific for the CTD of the largest subunit of RNAPII, and its activity is believed to be required to reactivate RNAPII, so that RNAPII can enter another round of transcription. We demonstrate that FCP1 is a phosphoprotein, and that phosphorylation regulates FCP1 activities. FCP1 is phosphorylated at multiple sites in vivo. The CTD phosphatase activity of phosphorylated FCP1 is stimulated by TFIIF, whereas dephosphorylated FCP1 is not. In addition to its role in the recycling of RNAPII, FCP1 also affects transcription elongation. Phosphorylated FCP1 is more active in stimulating transcription elongation than the dephosphorylated form of FCP1. We found that only phosphorylated FCP1 can physically interact with TFIIF. We set out to purify an FCP1 kinase from HeLa cells and identified casein kinase 2, which, surprisingly, displayed a negative effect on FCP1-associated activities.

ClpC of Bacillus subtilis is an ATP-dependent HSP100/Clp protein involved in general stress survival. A complex of ClpC with the protease ClpP and the adaptor protein Meca also controls competence development by regulated proteolysis of the transcription factor ComK. We investigated the in vitro chaperone activity of ClpC and found that the presence of Meca was crucial for the major chaperone activities of ClpC. In particular, Meca enabled ClpC to solubilize and refold aggregated proteins. Finally, in the presence of ClpP, Meca allowed the ClpC-dependent degradation of unfolded or heat-aggregated proteins. This study demonstrates that adaptor proteins like Meca through interaction with their cognate ClpC proteins can have a dual role in the protein quality-control network by rescuing, or together with ClpP, by degrading, aggregated proteins. Meca can thereby coordinate substrate targeting with ClpC activation, adding another layer to the regulation of HSP100/Clp protein activity.

Members of the protein family called ATPases associated with various cellular activities (AA[A.sup.+]) play a crucial role in transforming chemical energy into biological events. AA[A.sup.+] proteins are complex molecular machines and typically form ring-shaped oligomeric complexes that are crucial for ATPase activity and mechanism of action. The Escherichia coli transcription activator phage shock protein F (PspF) is an AA[A.sup.+] mechanochemical enzyme that functions to sense and relay the energy derived from nucleoside triphosphate hydrolysis to catalyze transcription by the [[sigma].sup.54]-RNA polymerase. Closed promoter complexes formed by the [[sigma].sup.54]-RNA polymerase are substrates for the action of PspF. By using a protein fragmentation approach, we identify here at least one [[sigma].sup.54]-binding surface in the PspF AA[A.sup.+] domain. Results suggest that ATP hydrolysis by PspF is coupled to the exposure of at least one [[sigma].sup.54]-binding surface. This nucleotide hydrolysis-dependent presentation of a substrate binding surface can explain why complexes that form between [[sigma].sup.54] and PspF are transient and could be part of a mechanism used generally by other AA[A.sup.+] proteins to regulate activity.

Epithelial tight junctions regulate paracellular permeability, restrict apical/basolateral intramembrane diffusion of lipids, and have been proposed to participate in the control of epithelial cell proliferation and differentiation. Previously, we have identified ZO-1-associated nucleic acid binding proteins (ZONAB), a Y-box transcription factor whose nuclear localization and transcriptional activity is regulated by the tight junction-associated candidate tumor suppressor ZO-1. Now, we found that reduction of ZONAB expression using an antisense approach or by RNA interference strongly reduced proliferation of MDCK cells. Transfection of wild-type or ZONAB-binding fragments of ZO-1 reduced proliferation as well as nuclear ZONAB pools, indicating that promotion of proliferation by ZONAB requires its nuclear accumulation. Overexpression of ZONAB resulted in increased cell density in mature monolayers, and depletion of ZONAB or overexpression of ZO-1 reduced cell density. ZONAB was found to associate with cell division kinase (CDK) 4, and reduction of nuclear ZONAB levels resulted in reduced nuclear CDK4. Thus, our data indicate that tight junctions can regulate epithelial cell proliferation and cell density via a ZONAB/ZO-1-based pathway. Although this regulatory process may also involve regulation of transcription by ZONAB, our data suggest that one mechanism by which ZONAB and ZO-1 influence proliferation is by regulating the nuclear accumulation of CDK4.

Mutations at the mouse microphthalmia locus (Mitf) affect the development of different cell types, including melanocytes, retinal pigment epithelial cells of the eye, and osteoclasts. The MITF protein is a member of the MYC supergene family of basic-helix-loop-helix-leucine-zipper (bHLHZip) transcription factors and is known to regulate the expression of cell-specific target genes by binding DNA as homodimer or as heterodimer with related proteins. The many mutations isolated at the locus have different effects on the phenotype and can be arranged in an allelic series in which the phenotypes range from near normal to white microphthalmic animals with osteopetrosis. Previous investigations have shown that certain combinations of Mitf alleles complement each other, resulting in a phenotype more normal than that of each homozygote alone. Here we analyze this interallelic complementation in detail and show that it is limited to one particular allele, [Mitf.sup.Mi-white] ([Mitf.sup.Mi-wh]), a mutation affecting the DNA-binding domain. Both loss- and gain-of-function mutations are complemented, as are other Mitf mutations affecting the DNA-binding domain. Furthermore, this behavior is not restricted to particular cell types: Both eye development and coat color phenotypes are complemented. Our analysis suggests that [Mitf.sup.Mi-wh]-associated interallelic complementation is due to the unique biochemical nature of this mutation.

The transcription factors WHITE COLLAR-1 (WC-1) and WHITE COLLAR-2 (WC-2) interact to form a heterodimeric complex (WCC) that is essential for most of the light-mediated processes in Neurospora crassa. WCC also plays a distinct non-light-related role as the transcriptional activator in the FREQUENCY (FRQ)/WCC feedback loop that is central to the N. crassa circadian system. Although an activator role was expected for WC-1, unanticipated phenotypes resulting from some wc-1 alleles prompted a closer examination of an allelic series for WC-1 that has uncovered roles for this central regulator in constant darkness and in response to light. We analyzed the phenotypes of five different wc-1 mutants for expression of FRQ and WC-1 in constant darkness and following light induction. While confirming the absolute requirement of WC-1 for light responses, the data suggest multiple levels of control for light-regulated genes.

Research has been conducted on genes for nitrous oxide reduction which are clustered on Pseudomonas aeruginosa chromosomes. Results demonstrate that nitrous oxide is the inducer molecule for the nos gene transcription.

Research has been conducted on Azotobacter vinelandii transcriptional activator NifA which is regulated by the NifL protein in response to nitrogen, carbon and redox status. Results suggest that different conformers of NifL may be generated in response to signal transduction events.

Research has been conducted on Escgerichia coli. The study of this bacterium carried out via the use of DNA microarray-based global transcript profiling in response to 4,5-dihydroxy-2-cyclopenten-1-one in investigating its antibacterial activity is described.

Members of the R/B basic helix-loop-helix (bHLH) family of plant transcription factors are involved in a variety of growth and differentiation processes. We isolated a dominant mutation in an R/B-related bHLH transcription factor in the course of studying Arabidopsis tryptophan pathway regulation. This mutant, atr2D, displayed increased expression of several tryptophan genes as well as a subset of other stress-responsive genes. The atr2D mutation creates an aspartate to asparagine change at a position that is highly conserved in R/B factors. Substitutions of other residues with uncharged side chains at this position also conferred dominant phenotypes. Moreover, overexpression of mutant atr2D, but not wild-type ATR2, conferred pleiotropic Effects, including reduced size, dark pigmentation, and sterility. Therefore, atr2D is likely to be an altered-function allele that identifies a key regulatory site in the R/B factor coding sequence. Double-mutant analysis with atr1D, an overexpression allele of the ATR1 Myb factor previously isolated in tryptophan regulation screens, showed that atr2D and atr1D have additive effects on tryptophan regulation and are likely to act through distinct mechanisms to activate tryptophan genes. The dominant atr mutations thus provide tools for altering tryptophan metabolism in plants.

Research has been conducted on recombinant Escherichia coli which produces human insulin-like growth factor I fusion protein. The transcriptosome profiles of E. coli have been investigated via the use of DNA microarrays, and the results demonstrate that transcriptosome profiling provides information for designing engineered strains with enhanced performance.

Research has been conducted on Spen proteins which regulate transcriptional effector expression in diverse signaling pathway. Results demonstrate that these proteins play important role in the transcriptional repression complex in both nuclear receptor and Notch signaling pathways.

Research has been conducted on serine/threonine kinase Pim-2. The authors reveal that Pim-2 is a direct link between growth factor-induced transcription and kinase-dependent pathway which promotes cell-autonomous survival.

The author reviews the publications on hexameric RNA/DNA helicase Rho required for transcriptional termination mechanisms in bacteria. The topics of interest include the analysis of organization of individual RNA-binding domains.

Research has been conducted on B-lymphocyte development which involves DNA rearrangements of immunoglobulin heavy and light chain loci. The authors report that B-cell development is arrested at the cycling pre-B-cell stage, and they propose that interferon regulatory factors-4,8 function as genetic switch to down-regulate surrogate light-chain gene expression and induce conventional light-chain gene transcription.

The author reviews the publications on RNA polymerase I transcription regulation in the nucleolus. The topics of interest include the initiation complex formation mechanism at the rDNA promoter, and the regulatory pathways adapting cellular rRNA synthesis to cell growth and metabolism.

Research has been conducted on chromatin structure which is important for the transcription regulation. The authors report that Drosophila FACT (facilitates chromatin transcription) is associated with GAGA factor via its subunit, binds to nucleotide and facilitates GAGA factor-directed chromatin remodeing.

Research has been conducted on ubiquitously expressed nuclear protein ALY which is involved in mRNA export from the nucleus to cytoplasm. The authors have investigated the structure of ALY's conserved RNA binding domain, and they report that this structure explains the interaction nature of the multifuntional proteins.

Research has been conducted on cyclin-dependent kinase Cdc28. The role of this kinase has been investigated via inhibition of its activity using conditional mutants which are sensitive to chemical inhibitors, and the results are reported.

Research has been conducted on DSIF and NELF which collaborate to inhibit elongation by RNA polymerase in human cell extracts. The roles of DSIF and NELF in promoter proximal pausing regulation at hsp70 promoter in Drosophila has been investigated, and the results are reported.

Research has been conducted on chromatin-remodeling activities in transcription. The role of these activities has been investigated in order to understand their interactions with transcriptional activators and their regulation of different transcription steps, and the results are reported.

The authors review the publications on transcription initiation. The topics of interest include the ability of tissue-specific and gene-selective core promoter complexes to regulate expressed genes responsible for such biological functions as DNA replication, germ cell maturation and organ development.

Research has been conducted on internal ribosome entry site within mRNA leader. The authors suggest that the structure of this entry site is dynamic, and that this RNA structure can be regulated via translational control.

Results indicate that the regulation of the two divergent promoters, argG and metY in Escherichia coli is simultaneously controlled by the cyclic AMP-cyclic AMP-catabolite activator protein complex and by arginine metabolism regulator, suggesting a link between carbon metabolism and protein synthesis.

Research has been conducted on genetic transcription at the onset of Bacillus subtilis sporulation which is regulated by Spo0A. The authors report that Spo0A functions after the intitial sporulation phase, and that it becomes a cell-specific transcription factor when sporangium is divided onto a forespore and mother cell.

Research has been conducted on transcription factor Myc which regulates downstream cellular responses. The authors have investigated a large-scale sceen for genomic Myc-binding sites in human cells via the use of bioinformatics, and they report that there is high regulatory and biological diversity among Myc-target genes.

Research has been conducted on tendons associated with the axial skeleton. The authors report that these tendons derive from somite fourth compartment, and that tendon primordia form in a location which must be connected by the mature tendonds.

Research has been conducted on Dpp/BMP morphogen in Drosophila. The authors have investigated the molecular events leading to Dpp/BMP morphogen primary response in Drosophila, and they report that this morphogen establishes finely tuned read-out of transcriptional repression.

Research has been conducted on human MTA3 product. The authors demonstrate that this product is an estrogen-dependent component of Mi-2/NuRD transcriptional corepressor in breast epithelial cells, and report that MTA3 is a key component of estrogen-dependent pathway which regulates differentiation and growth.

Research has been conducted on histone methylation which plays important role in eukaryotic gene expression regulation. Results demonstrate that histone methylation is a targeted event, and that it provides a mechanism by which histone methyltransferases could activate gene expression.

Research has been conducted on beta-globin. The authors describe their study of beta-globin gene activation molecular basis performed via the analysis of the factor recruitment and histone modification at the adult beta-globin gene.

Research has been conducted on ribonucleotide reductases which catalyse the synthesis of deoxyribonucleotides required for RNA repair and replication. The authors describe their study of these reductases carried out in accordance to their metal cofactors and organic radicals.

The circadian rhythms in Drosophila is regulated by two inter-locked transcriptional feedback loops. Research demonstrates that the second feedback loop is comprised of VRI and PDP1 proteins and the dClock, which confers rhythmic expression on dClock and other genes in the generation precise circadian rhythms.

Research has been conducted on Xanthobacter flavus LysR-type transcriptional regulator CbbR. The role of CbbR binding motifs in DNA binding via CbbR and transcriptional activation of the cbb promoter has been investigated, and the results are discussed.

Research has been conducted on methylo troph Methylobacterium extorquens AM1. The characterization of the M. extorquens AM1 gene which encodes LysR-type transcriptional regulator homologous to CbbR has been carried out, and the results demonstrate that it is serine cycle main regulator.

Research has been conducted on Salmonella enterica serovar Typhimurium. The role of hilD mutation in Salmonella strains which contain mutations in hilA negative regulators has been investigated, and the results are reported.