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Transcription Regulation (transcription + regulation)
Selected AbstractsLysine Acetylation: The Tale of a Modification from Transcription Regulation to MetabolismCHEMBIOCHEM, Issue 11 2010Mohammed Arif Dr. Reversible lysine acetylation is an important modification involved in the regulation of gene expression. Acetyl-CoA and NAD+ are major determinants of this modification, NAD+ levels being regulated by the cellular redox status. Recent reports have shown that lysine acetylation also regulates metabolic processes, thus linking the central metabolic process to gene expression. [source] Hansenula polymorpha Swi1p and Snf2p are essential for methanol utilisationFEMS YEAST RESEARCH, Issue 7 2004Paulina Ozimek Hansenula polymorpha; Peroxisomes; Transcription regulation; SWI/SNF complex Abstract We have cloned the Hansenula polymorpha SWI1 and SNF2 genes by functional complementation of mutants that are defective in methanol utilisation. These genes encode proteins similar to Saccharomyces cerevisiae Swi1p and Snf2p, which are subunits of the SWI/SNF complex. This complex belongs to the family of nucleosome-remodeling complexes that play a role in transcriptional control of gene expression. Analysis of the phenotypes of constructed H. polymorpha SWI1 and SNF2 disruption strains indicated that these genes are not necessary for growth of cells on glucose, sucrose, or various organic nitrogen sources which involve the activity of peroxisomal oxidases. Both disruption strains showed a moderate growth defect on glycerol and ethanol, but were fully blocked in methanol utilisation. In methanol-induced cells of both disruption strains, two peroxisomal enzymes involved in methanol metabolism, alcohol oxidase and dihydroxyacetone synthase, were hardly detectable, whereas in wild-type cells these proteins were present at very high levels. We show that the reduction in alcohol oxidase protein levels in H. polymorpha SWI1 and SNF2 disruption strains is due to strongly reduced expression of the alcohol oxidase gene. The level of Pex5p, the receptor involved in import of alcohol oxidase and dihydroxyacetone synthase into peroxisomes, was also reduced in both disruption strains compared to that in wild-type cells. [source] Transcription regulation of the Saccharomyces cerevisiae PIS1 gene by inositol and the pleiotropic regulator, Ume6pMOLECULAR MICROBIOLOGY, Issue 6 2008Niketa M. Jani Summary In Saccharomyces cerevisiae, transcription of most of the phospholipid biosynthetic genes (e.g. INO1, CHO1, CHO2 and OPI3) is repressed by growth in the presence of inositol and choline and derepressed in their absence. This regulation requires the Ino2p and Ino4p activators and the Opi1p repressor. The PIS1 structural gene is required for the synthesis of the essential lipid phosphatidylinositol. Previous reports show that PIS1 expression is uncoupled from inositol/choline regulation, but is regulated by carbon source, hypoxia and zinc. However, in this study we found that the expression of PIS1 is induced twofold by inositol. This regulation did not require Ino2p and Ino4p, although Ino4p was required for full expression. Ino4p is a basic helix-loop-helix protein that requires a binding partner. Curiously, none of the other basic helix-loop-helix proteins affected PIS1 expression. Inositol induction did require another general regulator of phospholipid biosynthesis, Ume6p. Ume6p was found to be a positive regulator of PIS1 gene expression. Ume6p, and several associated factors, were required for inositol-mediated induction and chromatin immunoprecipitation analysis showed that Ume6p directly regulates PIS1 expression. Thus, we demonstrate novel regulation of the PIS1 gene by Ume6p. [source] A role for eukaryotic translation initiation factor 2B (eIF2B) in taste memory consolidation and in thermal control establishment during the critical period for sensory developmentDEVELOPMENTAL NEUROBIOLOGY, Issue 6 2007Sharon Tirosh Abstract All species exhibit critical periods for sensory development, yet very little is known about the molecules involved in the changes in the network wiring that underlies this process. Here the role of transcription regulation of the translation machinery was determined by evaluating the expression of eIF2B,, an essential component of translation initiation, in both taste-preference development and thermal control establishment in chicks. Analysis of the expression pattern of this gene after passive-avoidance training revealed clear induction of eIF2B, in both the mesopallium intermediomediale (IMM) and in the striatum mediale (StM). In addition, a correlation was found between the concentration of methylanthranilate (MeA), which was the malaise substrate in the passive-avoidance training procedure, the duration of memory, and the expression level of eIF2B,. Training chicks on a low concentration of MeA induced short-term memory and low expression level of eIF2B,, whereas a high concentration of MeA induced long-term memory and a high expression level of eIF2B, in both the IMM and StM. Furthermore, eIF2B, -antisense "knock-down" not only reduced the amount of eIF2B, but also attenuated taste memory formation. In order to determine whether induction of eIF2B, is a general feature of neuronal plasticity, we checked whether it was induced in other forms of neuronal plasticity, with particular attention to its role in temperature control establishment, which represents hypothalamic-related plasticity. It was established that eIF2B, -mRNA was induced in the preopotic anterior hypothalamus during heat conditioning. Taken together, these results correlate eIF2B, with sensory development. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007. [source] Prokaryotic genome regulation: multifactor promoters, multitarget regulators and hierarchic networksFEMS MICROBIOLOGY REVIEWS, Issue 5 2010Akira Ishihama Abstract The vast majority of experimental data have been accumulated on the transcription regulation of individual genes within a single model prokaryote, Escherichia coli, which form the well-established on,off switch model of transcription by DNA-binding regulatory proteins. After the development of modern high-throughput experimental systems such as microarray analysis of whole genome transcription and the Genomic SELEX search for the whole set of regulation targets by transcription factors, a number of E. coli promoters are now recognized to be under the control of multiple transcription factors, as in the case of eukaryotes. The number of regulation targets of a single transcription factor has also been found to be more than hitherto recognized, ranging up to hundreds of promoters, genes or operons for several global regulators. The multifactor promoters and the multitarget transcription factors can be assembled into complex networks of transcription regulation, forming hierarchical networks. [source] Mapping of intrinsic bent DNA sites in the upstream region of DNA puff BhC4-1 amplified geneJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2001Adriana Fiorini Abstract We have identified bent DNA sites in the distal and proximal DNA puff BhC4-1 amplified gene promoter region of Bradysia hygida. The 2D modeling of the 3D DNA path and the ENDS ratio values calculated in this promoter region resulted in the identification of ten pronounced bent sites named BhC4B ,,9 to +,1. The 1847 bp fragment (,,3697 to ,,1850) in relation to the transcription start site shows multiple bending sites, BhC4B ,,9 to BhC4B ,,4, with periodicity ,300 bp. The analysis of the other identified bent region, starting at position ,,957, reveals that the BhC4B +,1 bent site colocalizes with the putative BhC4-1 minimal promoter. The sequence analysis of bent site BhC4B ,,4 shows a distribution of dA,dT at ,10 bp intervals between the middle of each tract, but intervals with more than one turn, ,20 bp, two helix turns, were detected in the other bent sites described here. The bent sites BhC4B ,,6 and BhC4B ,,4, contain two consensus sequences, with 60 bp each. The apparent molecular weight of fragments in the BhC4-1 promoter region were estimated in agarose gels and compared with the data obtained in polyacrylamide gels without and with ethidium bromide. The mobility reduction ratios (R -values) were determined, and a high R -value, 1.80, for a 1215 bp fragment in the distal promoter region and a 1.23 significant R -value for a 662 bp fragment in the proximal segment were found. To further analyze the predicted bent DNA sites in these fragments, the 2D trajectories of the 3D DNA path and other parameters, AT percentage, roll angle, ENDS ratio and ,G, were determined. The role of these bent sites in the BhC4-1 transcription regulation is discussed. © 2001 Wiley-Liss, Inc. [source] Age-related alterations of gene expression patterns in human CD8+ T cellsAGING CELL, Issue 1 2010Jia-Ning Cao Summary Aging is associated with progressive T-cell deficiency and increased incidence of infections, cancer and autoimmunity. In this comprehensive study, we have compared the gene expression profiles in CD8+ T cells from aged and young healthy subjects using Affymetrix microarray Human Genome U133A-2 GeneChips. A total of 5.2% (754) of the genes analyzed had known functions and displayed statistically significant age-associated expression changes. These genes were involved in a broad array of complex biological processes, mainly in nucleic acid and protein metabolism. Functional groups, in which down-regulated genes were overrepresented, were the following: RNA transcription regulation, RNA and DNA metabolism, intracellular (Golgi, endoplasmic reticulum and nuclear) transportation, signaling transduction pathways (T-cell receptor, Ras/MAPK, JNK/Stat, PI3/AKT, Wnt, TGF,, insulin-like growth factor and insulin), and the ubiquitin cycle. In contrast, the following functional groups contained more up-regulated genes than expected: response to oxidative stress and cytokines, apoptosis, and the MAPKK signaling cascade. These age-associated gene expression changes may be responsible for impaired DNA replication, RNA transcription, and signal transduction, possibly resulting in instability of cellular and genomic integrity, and alterations of growth, differentiation, apoptosis and anergy in human aged CD8+ T cells. [source] Yin yang 1 directly regulates the transcription of RE-1 silencing transcription factorJOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2008Lichun Jiang Abstract The RE-1 silencing transcription factor (REST) is a master transcription factor that plays a critical role in embryo development, especially during the process of neurogenesis and neural plasticity. However, the mechanism of REST gene transcription regulation is still an open question. Here, by combining bioinformatics analysis and experimental studies, we report that the transcription factor Yin Yang 1 (YY1) bound to a conserved YY1 binding site in the promoter of the mouse REST gene and positively regulated activity of this promoter in SH-SY5Y cells. Furthermore, analysis of microarray data revealed a significant correlation between the expression of YY1 and REST genes. Overall, this study suggests that YY1 directly regulates expression of the REST gene. © 2007 Wiley-Liss, Inc. [source] Transcriptional regulation of Foxp3 gene: Multiple signal pathways on the roadMEDICINAL RESEARCH REVIEWS, Issue 5 2009Zhu Shen Abstract Foxp3, forkhead/winged helix transcription factor 3, is a master transcription factor for the development and function of regulatory T cells. Foxp3 has been proved to be associated with immunoregulation, autoimmune diseases, infections, and tumor immune evasion/escape. Foxp3 regulates other critical gene transcriptions. However, the mechanism how the transcription of Foxp3 itself is regulated remains partly clear. In this article, we provided an overview of the current understanding of the transcriptional regulation of Foxp3 gene, including signaling pathways initiated by TCR, IL-2R/STAT pathway, TGF-,/Smad pathway, PI3K/Akt/mTOR axis, Notch signal pathway, IFN/IRF and IFN/nitric oxide axis, and epigenetic mechanisms. Some therapeutic agents on Foxp3 regulation were also reviewed. Points for attention in further study of Foxp3 transcription regulation, such as the combinations/cross-talks, the bi-directional functions, and species specificity of these pathways, were discussed as well. © 2009 Wiley Periodicals, Inc. Med Res Rev, 29, No. 5, 742,766, 2009 [source] Region 4 of , as a target for transcription regulationMOLECULAR MICROBIOLOGY, Issue 4 2003Simon L. Dove Summary Bacterial , factors play a key role in promoter recognition, making direct contact with conserved promoter elements. Most , factors belong to the ,70 family, named for the primary , factor in Escherichia coli. Members of the ,70 family typically share four conserved regions and, here, we focus on region 4, which is directly involved in promoter recognition and serves as a target for a variety of regulators of transcription initiation. We review recent advances in the understanding of the mechanism of action of regulators that target region 4 of ,. [source] Novel mode of transcription regulation by SdiA, an Escherichia coli homologue of the quorum-sensing regulatorMOLECULAR MICROBIOLOGY, Issue 5 2001Kaneyoshi Yamamoto SdiA, an Escherichia coli homologue of the quorum-sensing regulator, controls the expression of the ftsQAZ operon for cell division. Transcription of ftsQ is under the control of two promoters, upstream ftsQP2 and downstream ftsQP1, which are separated by 125 bp. SdiA activates transcription from ftsQP2 in vivo. Here, we demonstrate that SdiA facilitates the RNA polymerase binding to ftsQP2 and thereby stimulates transcription from P2. Gel shift and DNase I footprinting assays indicated that SdiA binds to the ftsQP2 promoter region between ,51 and ,25 with respect to the P2 promoter. Activation of ftsQP2 transcription by SdiA was observed with a mutant RNA polymerase containing a C-terminal domain (CTD)-deleted ,-subunit (,235) but not with RNA polymerase containing ,S or a CTD-deleted ,D (,D529). In good agreement with the transcription assay, no protection of P2 was observed with the RNA polymerase holoenzymes, E,S and E,D529. These observations together indicate that: (i) SdiA supports the RNA polymerase binding to ftsQP2; and (ii) this recruitment of RNA polymerase by SdiA depends on the presence of intact ,CTD. This is in contrast to the well-known mechanism of RNA polymerase recruitment by protein,protein contact between class I factors and ,CTD. In addition to the P2 activation, SdiA inhibited RNA polymerase binding to the ftsQP1 promoter and thereby repressed transcription from P1. Gel shift assays indicate weak binding of SdiA to the P1 promoter region downstream from ,13 (or +112 with respect to P2). Neither ,CTD nor ,CTD are required for this inhibition. Thus, the transcription repression of P1 by SdiA may result from its competition with the RNA polymerase in binding to this promoter. [source] Expansion of hematopoietic stem/progenitor cellsAMERICAN JOURNAL OF HEMATOLOGY, Issue 12 2008Wu Hai-Jiang Hematopoietic stem/progenitor cells (HSPCs) transplantation is hampered by the low number of stem cells per sample. To tackle this obstacle, several protocols for expansion of HSPCs in vitro are currently in development, such as the use of cytokine cocktails, coculture with mesenchymal stem cells as feeder cells, and cell culture in bioreactors. With the progress in the understanding of the molecular and cellular mechanisms regulating HSPCs maintenance and expansion, more recent approaches have involved transcription regulation, cell cycle regulation, telomerase regulation, and chromatin-modifying agents. The potential clinical application and safety issues relevant to the expanded HSPCs are also discussed in this review. Am. J. Hematol., 2008. © 2008 Wiley-Liss, Inc. [source] UV Exposure, Genetic Targets in Melanocytic Tumors and Transgenic Mouse Models,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 1 2005Frank R. de Gruijl ABSTRACT The genetic changes and corruption of kinase activity in melanomas appear to revolve around a central axis: mitogenic signaling along the RAS pathway down to transcription regulation by pRB. Epidemiological studies point to the importance of ultraviolet (UV) radiation in the etiology of melanoma, but where and how UV radiation is targeted to contribute to the oncogenic signaling remains obscure. Animal models of melanoma genesis could serve to clarify this issue, but many of these models are not responsive to UV exposure. Most interesting advances have been made by using transgenic mice that carry genetic defects that are known to be relevant to human melanoma: specifically, dysfunction in the tumor suppressive action of p161NK4a or a receptor tyrosine kinase/RAS pathway, that is constitutively activated in melanocytes. The latter types of mice appear to be most responsive to (neonatal) UV exposure. Whether this is due to a general increase in target cells by melanocytosis and a paucity or complete lack of pigment, or a possible UV-induced response of the promoter,enhancer of the transgene or a genuinely independent and additional genetic alteration caused by UV exposure needs to be established. Importantly, the full effect of UV radiation needs to be ascertained in mice with different pigmentation by varying the wavelengths, UV-B versus UV-A1, and the exposure schedules, i.e. neonatal versus adult and chronic versus intermittent overexposure. Intermittent UV-B overexposure deserves special attention because it most strongly evokes proliferative responses in melanocytes. [source] The MRG domain of human MRG15 uses a shallow hydrophobic pocket to interact with the N-terminal region of PAM14PROTEIN SCIENCE, Issue 10 2006Peng Zhang Abstract MRG15 is a transcription factor expressed in a variety of human tissues, and its orthologs have been found in many other eukaryotes which constitute the MRG protein family. It plays a vital role in embryonic development and cell proliferation, and is involved in cellular senescence. The C-terminal part of MRG15 forms a conserved MRG domain which is involved in interactions with the tumor suppressor protein retinoblastoma and a nucleoprotein PAM14 during transcriptional regulation. We report here the characterization of the interaction between the MRG domain of human MRG15 and PAM14 using both yeast two-hybrid and in vitro binding assays based on the crystal structure of the MRG domain. The MRG domain is predominantly hydrophobic, and consists of mainly ,-helices that are arranged in a three-layer sandwich topology. The hydrophobic core is stabilized by interactions among a number of conserved hydrophobic residues. The molecular surface is largely hydrophobic, but contains a few hydrophilic patches. Structure-based site-directed mutagenesis studies identified key residues involved in the binding of PAM14. Structural and biochemical data together demonstrate that the PAM14 binding site is consisted of residues Ile160, Leu168, Val169, Trp172, Tyr235, Val268, and Arg269 of MRG15, which form a shallow hydrophobic pocket to interact with the N-terminal 50 residues of PAM14 through primarily hydrophobic interactions. These results provide the molecular basis for the interaction between the MRG domain and PAM14, and reveal insights into the potential biological function of MRG15 in transcription regulation and chromatin remodeling. [source] Protein profiles of bovine placenta derived from somatic cell nuclear transferPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 16 2005Hong Rye Kim Abstract Practical application of animal cloning by somatic cell nuclear transfer (SCNT) has been hampered by an extremely low success rate. To address whether placental dysfunction in SCNT causes fetal loss during pregnancy, we have used a global proteomics approach using 2-DE and MS to analyze the differential protein patterns of three placentae from the afterbirth of cases of postnatal death, derived from SCNT of Korean Native cattle, and three normal placentae obtained from the afterbirth of fetuses derived from artificial insemination. Proteins within a pI range of 4.0,7.0 and 6.0,9.0 were analyzed separately by 2-DE in triplicate. A total of approximately 2000 spots were detected in placental 2-DE gels stained with CBB. In the comparison of normal and SCNT samples, 60 spots were identified as differentially expressed proteins, of which 33 spots were up-regulated proteins in SCNT placentae, while 27 spots were down-regulated proteins. Most of the proteins identified in this analysis appeared to be related with protein repair or protection, cytoskeleton, signal transduction, immune system, metabolism, extracellular matrix and remodeling, transcription regulation, cell structure or differentiation and ion transport. One of up-regulated proteins in SCNT was TIMP-2 protein known to be related to extracellular matrix and remodeling during pregnancy. Western blot analysis showed an increased level of TIMP-2 in SCNT placenta compared to normal. Our results revealed composite profiles of key proteins involved in abnormal placenta derived from SCNT, and suggested expression abnormality of these genes in SCNT placenta, resulting in fetal losses following SCNT. [source] BTB and TAZ domain scaffold proteins perform a crucial function in Arabidopsis developmentTHE PLANT JOURNAL, Issue 1 2009Hélène S. Robert Summary In Arabidopsis, bric-a-brac, tramtrack and broad (BTB) domain scaffold proteins form a family of 80 proteins that have involvement in various signaling pathways. The five members of the subfamily of BTB AND TAZ DOMAIN proteins (BT1,BT5) have a typical domain structure that is only observed in land plants. Here, we present a functional analysis of the BT family, of which at least four members are encoded by auxin-responsive genes. BT1 is a short-lived protein that is characteristically targeted for degradation by the 26S proteasome. Expression pattern, gene structure and sequence analyses indicate that BT1 and BT2 are closely related. They both localize to the nucleus and the cytosol, whereas the remaining BT proteins were determined as cytosolic proteins. Detailed molecular and phenotypic analysis of plants segregating for null mutations in the BT family revealed substantial redundancy among the BT members, and highlighted that BT proteins perform crucial roles in both male and female gametophyte development. BT2 seems to be the predominant gene in this process, in which it is functionally replaced by BT3 and BT1 through reciprocal transcription regulation. Compensational expression alters the steady-state mRNA levels among the remaining BT family members when other BT members are lost, and this contributes towards functional redundancy. Our data provide a surprising example of functional redundancy among genes required during gametophyte development, something that could not be detected in the current screens for gametophyte mutants. [source] Towards a new classification of ectodermal dysplasiasCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 4 2003J. Lamartine Summary Ectodermal dysplasias (EDs) constitute a large and complex group of diseases characterized by various defects in hair, nails, teeth and sweat glands. Of the 170 EDs described so far, fewer than 30 have been explained at the molecular level with identification of the causative gene. This review proposes a new classification of EDs based on the function of the protein encoded by the mutated gene. The EDs are reviewed in light of the recent molecular and biochemical findings and an attempt is made to classify ED causative genes into four major functional subgroups: cell,cell communication and signalling; adhesion; transcription regulation; and development. [source] | |||||||||||||||||||||||||