Transcription factor binding

Chromatin state provides a clear decipherable blueprint for maintenance of transcriptional patterns, exemplifying a mitotically stable form of cellular programming in dividing cells. In this regard, genomic studies of chromatin states within cancerous tissues have the potential to uncover novel aspects of tumor biology and unique mechanisms associated with disease phenotypes and outcomes.

15p vielonmusk 21-01-2022 14 1   Download

The main contents of this chapter include all of the following: Categories of activators, structures of the DNA-Binding motifs of activators, independence of the domains of activators, functions of activators, interaction among activators, regulation of transcription factors.

53p tangtuy05 30-03-2016 63 4   Download

Chapter 11 - general transcription factors in eukaryotes. Eukaryotic RNA polymerases, unlike their bacterial counterparts, are incapable of binding by themselves to their respective promoters. Instead, they rely on proteins called transcription factors to show them the way. Such factors are grouped into two classes: general transcription factors and gene-specifi c transcription factors (activators). In this chapter we will survey the general transcription factors that interact with all three RNA polymerases and their promoters.

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The Sp family is a family of transcription factors that bind to cis-elements in the promoter regions of various genes. Regulation of transcription by Sp proteins is based on interactions between a GC-rich binding site (GGGCGG) in DNA and C-terminal zinc finger motifs in the proteins. In this study, we characterized the GC-rich promoter of the gene for the DNA methyltransferase (Dnmt1) that is responsible for methylation of cytosine residues in mammals and plays a role in gene silencing.

10p system191 01-06-2013 38 4   Download

Selenoprotein P (SeP) is a plasma protein that contains up to 10 selenocysteine residues and accounts for about 50% of total selenium in human plasma. We have previously shown that SeP expression in the human liver cell line HepG2 is inhibited by transforming growth factor (TGF)-b1 on a transcriptional level. Smad proteins are the transcriptional mediators of TGF-b signalling and putative Smad-binding elements (SBE) comprising the core sequence CAGACA are present at two positions in the SeP promoter....

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The decoy approach against nuclear factor kB (NF-kB) is a useful tool to alter NF-kB dependent gene expression using synthetic oligonucleotides (ODNs) carrying NF-kB specific cis-elements. Unfortunately, ODNs are not stable and need to be extensively modified to be used in vivo or ex vivo. We have previously evaluated the possible use of peptide nucleic acids (PNAs) as decoy molecules. The backbone of PNAs is composed of N-(2-aminoethyl)glycine units, rendering these molecules resistant to both nucleases and proteases.

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Nuclear receptors (NRs) are ligand-regulated, DNA-binding transcription factors that function in the chromatin environment of the nucleus to alter the expression of subsets of hormone-responsive genes. It is clear that chromatin, rather than being a passive player, has a profound effect on both transcriptional repression and activation mediated by NRs.

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Wilson disease (WD), an inherited disorder affecting copper metabolism, is characterized by hepatic cirrhosis and neuronal degeneration, which result from toxic levels of copper that accumulate in the liver and brain, respectively. We reported previously that the  1.3-kb promoter of the WD gene contains four metal response elements (MREs). Among the four MREs, MREa plays the most important role in the transcriptional activation of the WD promoter.

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Retinoids are potent immune modulators that inhibit Fas ligand (FasL) expression and thereby repress the activationinduced apoptosis of immature thymocytes and T-cell hybridomas. In this study, we demonstrate that all-transretinoic acid (all-trans-RA) directly represses the transcriptional activity of the nuclear factors of activated T-cells (NFAT), which is an important transactivator of the FasL promoter.

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Heat shock transcription factors (HSFs) are characterized by their ability, upon activation, to bind to heat shock response elements (HSE) present in the promoter of their target genes. HSE are composed of inverted repeats of the pentamer nGAAm. In this study, we compare the embryonic HSF2 protein, purified from F9 embryonal carcinoma cells tumor, and thein vitro synthesized HSF2. We show that the context of HSF2 synthesis influences its thermosensitivity and DNA-binding properties.

11p research12 29-04-2013 47 2   Download

Chickenovalbuminupstreampromoter-transcriptionfactorI (COUP-TFI, or NR2F1) is an orphan nuclear receptor that plays amajor role in the development of the nervous system. We show here that three ETS response elements in the COUP-TFIpromoter mediate its transcription. A reporter gene containing theseETSbinding sites is activatedbyEts-1, while the same reporter with point mutations on all three ETS response elements is not.

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Erythroid dematin is a major component of red blood cell junctional complexes that link the spectrin±actin cytoskel-eton to the overlying plasma membrane. Transcripts of dematinarewidelydistributed includinghumanbrain, heart, lung, skeletalmuscle, andkidney.Invitro, dematinbinds and bundles actin ®laments in a phosphorylation-dependent manner. The primary structure of dematin consists of a C-terminal domain homologous to theÔheadpieceÕ domain of villin, an actin-binding protein of the brush border cyto-skeleton. ...

12p research12 23-04-2013 42 3   Download

Virus infection results in the activation of a set of cellular genes involved in host antiviral defense. IRF-3 has been identifiedas a critical transcription factor in this process. The activationmechanismof IRF-3 is not fully elucidated,yet it involves a conformational change triggered by the virus-dependent phosphorylation of its C-terminus. This con-formational change leads to nuclear accumulation,DNA binding and transcriptional transactivation.

10p tumor12 22-04-2013 38 3   Download

Eos is a zinc finger transcription factor of the Ikaros family. It binds typical GGGAA Ikaros recognition sites in DNA and functions as a transcriptional repressor. Here we show that Eos associates with the corepressor C-terminal-binding protein (CtBP). CtBP has previously been shown to bind Pro-X-Asp-Leu-Ser (PXDLS) motifs in several DNA-binding proteins. We note that Eos contains a relatedmotif PEDLA, and we demonstrate that CtBP can bind this site weakly but that it also contacts additional regions of Eos....

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The matrix metalloproteinase (MMP) family degrades the extracellular matrix. One member of this family, MMP-1, initiates the breakdown of interstitial collagens. The expression ofMMP-1 is controlled by themitogen activated protein kinase (MAPK) pathway(s) via the activity of acti-vator protein-1 (AP-1) and polyoma enhancing activity-3/ E26 virus (PEA3/ETS) transcription factors through con-sensus binding sites present in the promoter.

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We have isolated and studied the cloned sigma factors SASIG1-3 from mustard (Sinapis alba). In functional ana-lyses using both promoter and factor mutants,the three recombinant proteins all had similar basic properties but also revealed differences in promoter preference and requirements for single nucleotide positions. Directedmuta-genesis of SASIG1 identified critical residues within the conserved regions 2.4 and 4.2 necessary for binding of the )10 and)35 promoter elements,respectively.

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Induction of CYP3A genes by the ligand-activated preg-nane-X-receptor (PXR)involves the interaction of other as yet unidentified liver transcription factors. Here we show that the CYP3A1promoter contains two active sites con-trolled by the CCAAT/enhancer-binding protein a (C/ EBPa), previously shown to regulate a number of liver stress response genes. We have identified two functional C/EBP binding sites at theCYP3A1promoter that confer luciferase activity to C/EBPacotransfected CHO cells.

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The interaction of aThermus thermophilustmRNA tran-script with alanyl-tRNA synthetase and elongation factor Tu has been studied. The synthetic tmRNA was found to be stable up to 70
C. The thermal optimum of tmRNA alanylation was determined to be around 50
C. At 50
C, tmRNA transcript was aminoacylated by alanyl-tRNA synthetase with 5.9times lower efficiency (kcat /Km) than tRNA Ala , primarily because of the difference in turnover numbers (kcat ).

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Synaptophysin, one of the major proteins on synaptic vesi-cles, is ubiquitously expressed throughout the brain. Syn-aptophysin and synapsin I, another synaptic vesicle protein, are also expressed by retinoic acid-induced neuronally dif-ferentiated P19 teratocarcinoma cells. Here, we show that inhibition of histone deacetylase activity in P19 cells is suf-ficient to activate transcription of the synaptophysin and synapsin I genes, indicating that neuronal differentiation and impairment of histone deacetylases results in a similar gene expression pattern....

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TheroleoftheSaccharomyces cerevisiae Pip2p–Oaf1p transcription factor was examined in reference to the regu-lation of the peroxin gene PEX25involved in peroxisome proliferation. The PEX25promoter contains an oleate response element (ORE)-like sequence comprising a CGG palindrome lacking a canonical adenine, which is considered critical for element function and Pip2p–Oaf1p binding. Pex25p levels were higher in wild-type cells grown on oleic acid medium than in those grown on ethanol, but this induction was abolished in cells devoid of Pip2p–Oaf1p....

10p fptmusic 16-04-2013 58 3   Download