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Results for “Enhancer mapping”

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PubMed2001

Individual 'fingerprints' in human sleep EEG topography.

The sleep EEG of eight healthy young men was recorded from 27 derivations during a baseline night and a recovery night after 40 h of waking. Individual power maps of the nonREM sleep EEG were calculated for the delta, theta, alpha, sigma and beta range. The comparison of the normalized individual maps for baseline and recovery sleep revealed very similar individual patterns within each frequency band. This high correspondence was quantified and statistically confirmed by calculating the Manhattan distance between all pairs of maps within and between individuals. Although prolonged waking enhanced power in the low-frequency range (0.75-10.5 Hz) and reduced power in the high-frequency range (13.25-25 Hz), only minor effects on the individual topography were observed. Nevertheless, statistical analysis revealed frequency-specific regional effects of sleep deprivation. The results demonstrate that the pattern of the EEG power distribution in nonREM sleep is characteristic for an individual and may reflect individual traits of functional anatomy.

Adult↗

PubMed1998

The Neurospora aab-1 gene encodes a CCAAT binding protein homologous to yeast HAP5.

The expression of the am (glutamate dehydrogenase) gene is dependent upon two upstream activating sequences, designated URSam(alpha) and URSam(beta). A heteromeric nuclear protein Am Alpha Binding protein (AAB) binds specifically to a CCAAT box within the URSam(alpha) element. AAB appears to be composed of three components. We used polyclonal antiserum raised against the highly purified AAB1 subunit to isolate a partial aab-1 cDNA clone, which was then used to isolate a full-length cDNA and a genomic clone. The full-length cDNA has the potential to encode a 272 amino acid protein with a calculated molecular weight of 30 kD. Amino acid sequence obtained by Edman analysis of the AAB1 protein confirmed that the aab-1 gene had been cloned. AAB-1 shows similarity to the HAP5 protein of yeast and the CBF-C protein of rat. Each of these proteins is an essential subunit of their respective heteromeric CCAAT binding proteins. The aab1 gene maps on linkage group III of Neurospora crassa near the trp-1 locus. Disruption of the aab-1 gene results in pleiotropic effects on growth and development as well as a 50% reduction in glutamate dehydrogenase levels. Transformation of the aab-1 disruption mutant strain with the cloned genomic copy of the aab-1 gene rescued all of the phenotypic alterations associated with the aab-1 mutation.

Base Sequence↗

PubMed2005

Differentiation between solitary brain metastasis and high-grade glioma by diffusion tensor imaging.

We tested our hypothesis that fractional anisotropy (FA) maps of diffusion tensor imaging could be used to differentiate between a solitary brain metastasis and a high-grade glioma. In seven patients with a solitary metastasis and seven patients with a high-grade glioma, FA values of enhancing and non-enhancing parts of the tumour were compared. Additionally, we visually assessed FA maps. No significant difference in the FA values of either the enhancing or non-enhancing part was found between the two groups. In the visual assessment, displacement of subcortical white-matter fibres was found in five of the seven metastasis patients, but in only one glioma patient. Additionally, discrimination between tumour and oedema was possible in three of the seven metastasis patients, but not in any glioma patient. Although FA values are not helpful in differentiating between the two groups, visual differences in FA values can allow the differentiation. Displacement of white-matter fibres is another finding suggestive of metastasis.

Adolescent↗

PubMed2001

Oligomerization mediated by a helix-loop-helix-like domain of baculovirus IE1 is required for early promoter transactivation.

IE1 is a principal transcriptional regulator of Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV). Transactivation by IE1 is stimulated when early viral promoters are cis linked to homologous-region (hr) enhancer sequences of AcMNPV. This transcriptional enhancement is correlated with the binding of IE1 as a dimer to the 28-bp palindromic repeats comprising the hr enhancer. To define the role of homophilic interactions in IE1 transactivation, we have mapped the IE1 domains required for oligomerization. We report here that IE1 oligomerizes by a mechanism independent of enhancer binding, as demonstrated by in vitro pull-down assays using fusions of IE1 (582 residues) to the C terminus of glutathione S-transferase. In vivo oligomerization of IE1 was verified by immunoprecipitation of IE1 complexes from extracts of plasmid-transfected SF21 cells. Analyses of a series of site-directed IE1 insertion mutations indicated that a helix-loop-helix (HLH)-like domain extending from residue 543 to residue 568 is the primary determinant of oligomerization. Replacement of residues within the hydrophobic face of the putative dimerization domain disrupted IE1 homophilic interactions and caused loss of IE1 transactivation of hr-dependent promoters in plasmid transfection assays. Thus, oligomerization is required for IE1 transcriptional stimulation. HLH mutations also reduced IE1 stability and abrogated transactivation of non-hr-dependent promoters. These data support a model wherein IE1 oligomerizes prior to DNA binding to facilitate proper interaction with the symmetrical recognition sites within the hr enhancer and thereby promote the transcription of early viral genes.

Binding Sites↗

PubMed1994

A topographical analysis of spectral electromyographic data of the human masseter muscle under different functional conditions in healthy subjects.

In 20 healthy subjects, 16-channel surface electromyograms (EMG) were recorded with the mandible in its postural position, during compensation for forces applied from ipsilateral, contralateral and frontal positions, and during force-constant biting on a unilaterally placed force transducer. After artefact elimination, EMG power spectra were calculated on the basis of the original EMG curves via fast Fourier transformation. Using spectral EMG characteristics, EMG maps were computed by means of an interpolation algorithm and an imaging procedure. Spectral EMG maps were demonstrated for all the test conditions. Significant differences of myoelectrical activity were verified between the 16 electrode positions. Moreover, the levels and/or the topographical distributions of spectral EMG powers differed significantly between the test conditions. During biting as well as with contralaterally and frontally applied forces, the highest EMG activity was found in the inferior third of the masseter and the lowest in the superior third. With ipsilaterally applied forces, the topographical distribution of the total EMG power was completely changed. The power maximum was frequently demonstrated in the superior, especially the posterosuperior, third of the muscle, the minimum in the inferior third. In the postural position of the mandible, EMG activity decreased from the anterior to the posterior regions of the masseter. If the bite force or the horizontally applied forces were enhanced, EMG activity increased significantly but the EMG map structures were only changed in some details. The topographical distribution of myoelectrical activity demonstrated by EMG maps characterizes the intramuscular activation patterns of distinct masseter functions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1997

Transcriptional regulation of OCI-5/Glypican 3: elongation control of confluence-dependent induction.

OCI-5/Glypican 3, a member of the glypican family of proteoglycans, is the defective gene in the Simpson-Golabi-Behmel overgrowth syndrome. OCI-5 expression is developmentally regulated in the intestinal epithelium, and the mechanism of its regulation was studied in the rat intestinal epithelial cell line IEC-18. A large induction of OCI-5 transcript and protein was observed at high cell density. Among other glypican family members, kappa-glypican also exhibited a confluence-dependent induction in select cell types. Nuclear run-on analysis indicated that cell-density regulation of OCI-5 occurs at the level of transcription. The rat and mouse OCI-5 promoters were cloned and found to be highly conserved, located within CpG islands and contain regions of alternating purine and pyrimidine residues. No TATA-box or recognizable INR element was observed. Consensus binding sites for AP-2, SP-1, zeste and NF-1/CTF are conserved across human, mouse and rat promoters. 5' deletion mapping of the rat promoter identified regions which enhance and repress promoter activity, with no apparent confluence-dependence or tissue-specificity. Nuclear run-on analysis probing different regions of the gene suggests that elongation control plays a role in the induction of OCI-5 by confluence.

Animals↗

PubMed1990

Negative and positive cis-acting elements control the expression of murine alpha 1-protease inhibitor genes.

The alpha 1-protease inhibitor (alpha 1-PI) proteins of mice are encoded by a group of genes whose members are expressed coordinately in a liver-abundant pattern and are regulated primarily at the transcriptional level. To better understand the developmental and tissue-specific regulation of this gene family, one member that is analogous to the human alpha 1-antitrypsin gene was chosen for study. Deletional analysis of the upstream regulatory region of this gene was performed, spanning from -10 kilobases to -80 base pairs relative to the transcriptional start site. Two functional positive cis-acting elements within the 522 bases immediately upstream of the start site for transcription were shown to modulate the level of expression from this promoter when introduced into human or mouse hepatoma cells, and a third region acted as a negative regulatory element in that its deletion resulted in a two- to sixfold increase of expression of a transfected minigene construct. Sequence comparison between the regulatory domains of two mouse alpha 1-PI genes and the human alpha 1-antitrypsin gene showed that the mouse gene contains a novel positive cis-acting element which is absent in human gene and that a specific eight-base-pair difference between species results in a strong positive cis-acting element in the human gene acting as a negative element in the mouse gene. An enhancer located approximately 3,000 base pairs upstream of the major start site for transcription was also identified. This element is position and orientation independent. Several different DNA-protein binding assays were used to demonstrate that each DNA segment with functional significance in transfection assays interacts specifically with proteins found in adult mouse liver nuclei. The major positive-acting element appeared to be specifically recognized by nuclear proteins found only in tissues that express alpha 1-PI, while the negative element binding proteins were ubiquitous. Thus, the distal regulatory domain including bases -3500 to -133 of this murine alpha 1-PI gene family member is more complex than was previously demonstrated. It is composed of a set of at least three additional functional cis-acting regulatory elements besides those which have been mapped by others and has a far upstream enhancer.

Amino Acid Sequence↗

PubMed1996

A screen for genes that function downstream of Ras1 during Drosophila eye development.

Cell-fate specification of the R7 photoreceptor cell is controlled by the sevenless receptor tyrosine kinase (SevRTK) and Ras1, the Drosophila homologue of mammalian H-ras, K-ras and N-ras oncogenes. An activated form of Ras1 expressed under control of the sevenless enhancer/promoter (sev-Ras1V12) induces production of supernumerary R7 photoreceptor cells, which causes the eye to become rough in appearance. To isolate mutations in genes functioning downstream of Ras1, we carried out a screen for dominant suppressors and enhancers of this rough eye phenotype. Approximately 850,000 mutagenized flies were screened, and 282 dominant suppressors and 577 dominant enhancers were isolated. Mutations in the Drosophila homologues of Raf, MEK, MAPK, type I Geranylgeranyl Transferase and Protein Phosphatase 2A were isolated, as were mutations in several novel signaling genes. Some of these mutant genes appear to be general signaling factors that function in other Ras1 pathways, while one seems to be more specific for photoreceptor development. At least two suppressors appear to function either between Ras1 and Raf or in parallel to Raf.

Animals↗

PubMed1990

Transcription of the human calcitonin gene is mediated by a C cell-specific enhancer containing E-box-like elements.

The calcitonin (CT) gene is expressed normally in thyroidal C-cells and in a restricted population of cells in the central and peripheral nerve system. To define the cis-elements within the 5'-flanking DNA of the human CT gene which mediate this cell-specific expression, we used DNA transfer techniques and a transient transfection approach. We found that a DNA sequence located between -1290 and -820 of the CT 5'-flanking DNA functioned as an enhancer of basal transcription in C-cells (from medullary thyroid carcinoma) but not in rat glioma (C6), hamster insulinoma (HIT), fibroblasts (3T3), or epithelial cells (HeLa and CV1). Further mapping revealed the presence of at least two elements within the enhancer region; an upstream element (USE, located between -1060 and -1030) which could not function independently but its removal caused 70-80% loss of enhancer activity and a downstream element (DSE, located at -1033 to -920) which functioned independently as a cell-specific enhancer but with reduced activity. The binding pattern of nuclear proteins from C-cells to the enhancer elements was studied by an electrophoretic mobility shift assay. A protein-DNA complex was formed with the USE which could be competed, specifically, by an oligonucleotide containing the microE2 motif of the immunoglobulin gene enhancer. A similar complex was formed with the DSE fragment. Nuclear proteins from HeLa cells failed to form complexes with USE. Moreover, the binding pattern of proteins derived from HeLa cells to DSE was different from that of C-cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Identification of cis-regulatory elements required for larval expression of the Drosophila melanogaster alcohol dehydrogenase gene.

The Alcohol dehydrogenase (Adh) genes of two distantly related species, Drosophila melanogaster and Drosophila mulleri, display similar, but not identical, patterns of tissue-specific expression in larvae and adults. The regulatory DNA sequences necessary for wild-type Adh expression in D. mulleri larvae were previously reported. In this paper we present an analysis of the DNA sequences necessary for wild-type Adh expression in D. melanogaster larvae. We show that transcription from the proximal promoter of the melanogaster Adh gene is regulated by a far upstream enhancer and two or more elements near the transcription start site. The enhancer is tissue specific and stimulates transcription to high levels in fat body and to lower levels in midgut and malpighian tubules whether linked to the proximal promoter or to a heterologous promoter. The enhancer activity localized to at least two discrete regions dispersed over more than 1.7 kb of DNA. Deletion of any one of these subregions reduces Adh transcription in all three larval tissues. Similarly, two regions immediately upstream of the proximal promoter start site are necessary for wild-type transcription levels in all three tissues. Thus, each of the identified regulatory elements is sufficient for low levels of Adh gene expression in all three larval tissues, but maximal levels of expression requires the entire set.

Adipose Tissue↗

PubMed2003

Identification of herpes simplex virus type 1 latency-associated transcript sequences that both inhibit apoptosis and enhance the spontaneous reactivation phenotype.

The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) gene is essential for the high spontaneous and induced reactivation phenotype of HSV-1 in the rabbit ocular model and for the high induced reactivation phenotype in the mouse ocular model. Recently we showed that LAT has an antiapoptosis function, and we hypothesized that LAT's ability to inhibit apoptosis played an important role in LAT's ability to enhance the reactivation phenotype. Expression of just the first 1.5 kb of the 8.3-kb LAT gene is sufficient for both inhibition of apoptosis in an in vitro transient-transfection assay and the high spontaneous reactivation phenotype in vivo. Here we show the results of more complex mapping studies in which inhibition of apoptosis and the enhanced spontaneous reactivation phenotype also appear to be linked. The HSV-1 mutant virus dLAT371 has a high spontaneous reactivation phenotype in rabbits, suggesting that the LAT region deleted in this mutant (LAT nucleotides 76 to 447) is not required for this phenotype. The LAT3.3A viral mutant (which expresses LAT nucleotides 1 to 1499) also has a high spontaneous reactivation phenotype, suggesting that the region of LAT not expressed by this mutant (LAT nucleotide 1500 to the end of LAT) is also not required for this phenotype. Surprisingly, LAT2.9A, which is a combination of dLAT371 and LAT3.3A (i.e., it expresses LAT nucleotides 1 to 76 and 447 to 1499), has a low spontaneous reactivation phenotype indistinguishable from that of LAT null mutants. We report here that consistent with the low spontaneous reactivation phenotype of LAT2.9A, a plasmid expressing the identical LAT RNA did not inhibit caspase 9-induced apoptosis. In contrast, plasmids containing the same deletion but able to transcribe up to or past LAT nucleotide 2850 (rather than just up to LAT nucleotide 1499) inhibited caspase 9-induced apoptosis, consistent with the high spontaneous reactivation phenotype of dLAT371. Thus, LAT2.9A may have a low spontaneous reactivation phenotype because the LAT RNA that is made cannot block apoptosis, and dLAT371 apparently has a high spontaneous reactivation phenotype because the LAT RNA made has significant antiapoptosis activity. Furthermore, LAT appeared to have at least two regions capable of interfering with caspase 9-induced apoptosis. One region partially overlaps LAT nucleotides 76 to 447. The second region is partially (or completely) downstream of LAT nucleotide 1499.

Animals↗

PubMed1995

Effects of ONO-1078, a leukotriene antagonist, on cardiovascular responses induced by vagal stimulation, capsaicin, and substance P in guinea pigs.

AIM: To determine the role of ONO-1078, 4-oxo-8 -[p-(4-phenylbutyloxy) benzoylamino]- 2-(tetrazol-5-yl) -4H-1-benzopyran hemihydrate, in cardiovascular responses induced by vagal stimulation, capsaicin, and substance P. METHODS: Evans blue extravasation in the atrium and ventricle, and mean arterial pressure (MAP) were observed. RESULTS: Electric stimulation of vagus (ESV, 10 Hz, 5 ms, 2 or 10 V, for 90 s) increased Evans blue extravasation in the hearts of atropine (1 mg.kg-1, i.v.)-pretreated guinea pigs. Capsaicin (0.05 mg.kg-1, i.v.) and substance P (1 microgram.kg-1, i.v.) enhanced the dye extravasation and elicited a drop in MAP. ONO-1078 (0.03 and 0.1 mg.kg-1, i.v.) inhibited ESV-induced response, especially at stimulation of 2 V. ONO-1078 (0.03 mg.kg-1) attenuated capsaicin-induced cardiac microvascular leakage and hypotensive response, but failed to inhibit substance P-induced responses. CONCLUSION: ONO-1078 can modulate the cardiovascular responses in neurogenic inflammation, possibly mediated by inhibiting sensory neuropeptide release.

Animals↗

PubMed2000

Cell wall perturbation in yeast results in dual phosphorylation of the Slt2/Mpk1 MAP kinase and in an Slt2-mediated increase in FKS2-lacZ expression, glucanase resistance and thermotolerance.

The protein kinase C (PKC1) pathway is essential for maintaining cell integrity in yeast. Here it is shown that various forms of cell wall damage result in activation of the downstream MAP kinase Slt2/Mpk1. Several cell wall mutants displayed enhanced FKS2-lacZ expression, a known output of Slt2 activation. A similar response was obtained with wild-type cells grown in the presence of the cell wall perturbants Calcofluor white and Zymolyase. Upregulation of FKS2-lacZ in response to sublethal concentrations of these agents fully depended on the presence of Slt2. The same cell wall stress conditions resulted in dual threonine and tyrosine phosphorylation of Slt2. Both Slt2 phosphorylation and FKS2-lacZ induction could be largely prevented by providing osmotic support to the plasma membrane. Interestingly, Slt2 phosphorylation in response to cell wall damage required the putative plasma-membrane-located sensor Mid2 but not Hcs77/Wsc1. Finally, cell wall perturbation gave rise to cells with increased resistance to glucanase digestion and heat shock. These responses depended on the presence of Slt2. These results indicate that weakening of the cell wall activates the Slt2/Mpk1 MAP kinase pathway and results in compensatory changes in the cell wall.

Benzenesulfonates↗

PubMed1972

An enhancing role for DNA synthesis in formation of bacteriophage lambda recombinants.

Recombination in some intervals of the map of phage lambda is associated with more DNA synthesis than in other intervals. Blockage of DNA synthesis by high temperature in a host temperature-sensitive for DNA synthesis results in the relative reduction of recombinant frequencies in those regions having the larger amounts of recombination-associated synthesis. Reduction of DNA synthesis at normal temperatures by a combination of the bacterial mutation and a mutation in one of the phage genes required for DNA synthesis has the same consequence. Therefore, DNA synthesis enhances recombinant particle formation more in some map intervals than in others.

Centrifugation, Density Gradient↗

PubMed1998

Enhancement of ventricular gradient variability during acute myocardial ischemia.

We evaluated the influence of local myocardial ischemia induced by experimental coronary stenosis on the ventricular gradients (VGs) and determined whether changes of VG were related to the alterations of monophasic action potentials (MAPs). The coronary flow was reduced to 50% in the left anterior descending coronary artery for 30 min in nine dogs. The VG and MAP of consecutive heartbeats over a 20-s interval were obtained from McFee and Parungao body surface leads and a suction electrode on the ischemic and non-ischemic regions. The coefficients of variation of VG and MAP parameters were calculated as indices of variability. The coefficients of variation of the VG magnitude and the MAP area in the ischemic region were greater at 5 min after partial occlusion than in the control period (P < 0.05, P < 0.01, respectively). There was a significant correlation between the coefficient of variation of the VG magnitude and the coefficient of variation of the MAP area in the ischemic region (r = 0.707, P < 0.0001 ) but not in the non-ischemic region. VG variability was enhanced during acute regional ischemia of the ventricular myocardium. VG variability may be caused by enhanced electrical alteration of the MAP in ischemic myocardium.

Action Potentials↗

PubMed1994

The human junD gene is positively and selectively autoregulated.

The junD gene is much less inducible than that of the two other members of the jun family; c-jun and junB, and is constitutively expressed in most tissues. We cloned the promoter of the human junD (hjunD) gene and found that it contains multiple cis-acting elements, most of which are conserved from chicken to human. Those included the TATA box, TRE, the CAAT box (referred to as the CTT complex), CREs, an Oct motif, and a number of GC boxes, most probably the recognition site for the SP1 transcription factor. The enhancer of the gene was localized to the -83 to -194 region that contains a GC box and an Oct motif. The CTT complex is shared by the promoters of the three jun genes, but each with a unique TRE. We show here that the hjunD TRE binds proteins that are related, but not identical, to the classical AP1 complex. We demonstrate by transfection experiments that the hjunD promoter is preferentially regulated by hjunD, through its unique TRE, generating a positive autoregulatory loop that might be responsible for its constitutive expression.

Animals↗

PubMed1977

The origin of ventricular arrhythmias 24 hours following experimental anterior septal coronary artery occlusion.

The anterior septal coronary artery was acutely ligated in 16 open-chest anesthetized dogs to produce an infarct of the septal myocardium. Twenty-four hours following occlusion complete epicardial mapping and extensive plunge electrode recording techniques were used to localize the sites of origin and patterns of activation of the ventricular tachyarrhythmias that developed during recovery. The earliest electrical activity for 13 individual rhythms was recorded from surviving septal subendocardial Purkinje fibers at the margins of the infarct, in the right or left ventricle, directly underlying the sites of earliest epicardial breakthrough. The sites of origin were verified by demonstrating unchanged activation sequences during pacing through the electrode sites which recorded the earliest activity. None of the arrhythmias arose from the His bundle or bundle branches despite the fact that these tissues course directly through the necrotic septum. The data presented supports the hypothesis that ventricular arrhythmias occuring in the 24-36 hour post acute infarction period may originate in the surviving subendocardial Purkinje system. Our experimental model shows that in cases in which a malignant rhythm arises from a focus, whether it is due to enhanced automaticity or local re-entry, epicardial mapping alone may not identify the source of the arrhythmias. Extensive endocardial mapping may provide a more rational basis for surgical interventions designed to abolish these arrhythmias.

Animals↗

PubMed1985

Active T-cell receptor genes have intron deoxyribonuclease hypersensitive sites.

The T-cell receptor beta-chain gene has a nuclease hypersensitive site in several kinds of T cells, which does not appear in B cells expressing immunoglobulins. Conversely, the kappa immunoglobulin gene shows a known hypersensitive site at its enhancer element in B cells, as expected, but this site is absent in T cells. As is the case with immunoglobulin genes, the T-cell receptor site lies within the gene, in the intron separating joining and constant region segments. These nuclease hypersensitive DNA configurations in the introns of active T-cell receptor and immunoglobulin genes may arise from control elements that share ancestry but have diverged to the extent that each normally acts only in lymphoid cells which use the proximal gene product.

Animals↗