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PubMed2005

Tissue specificity of hedgehog repression by the Polycomb group during Drosophila melanogaster development.

During embryogenesis and wing disc morphogenesis in Drosophila, different developmental mechanisms are used along the antero-posterior (A-P) axis. The establishment of antero-posterior polarity requires the secreted protein Hedgehog, which is only expressed in P compartments and which is a key effector of the Engrailed transcription factor. At the same time, it is essential that both engrailed and hedgehog (hh) remain in a repressed state in A compartments. In this article, we show that hh is maintained in a repressed state by the Polycomb group (PcG) chromatin proteins. We show that this process takes place during embryogenesis through two genomic elements that display genetic properties of a PRE. Interestingly, hh expression is not regulated by PcG genes in salivary glands, although at the same developmental stage PcG proteins repress hh in the A compartment of the wing disc. In addition, no PcG binding sites were found on polytene chromosomes, neither within hh transgenic constructs nor at the hh endogenous locus. Together, these results suggest that hh repression by the PcG acts in a tissue-specific manner.

Animals↗
PubMed2006

Dephosphorylation and genome-wide association of Maf1 with Pol III-transcribed genes during repression.

Nutrient deprivation and various stress conditions repress RNA polymerase III (Pol III) transcription in S. cerevisiae. The signaling pathways that relay stress and nutrient conditions converge on the conserved protein Maf1, but how Maf1 integrates environmental conditions and couples them to transcriptional repression is largely unknown. Here, we demonstrate that Maf1 is phosphorylated in favorable conditions, whereas diverse unfavorable conditions lead to rapid Maf1 dephosphorylation, nuclear localization, physical association of dephosphorylated Maf1 with Pol III, and Maf1 targeting to Pol III-transcribed genes genome wide. Furthermore, Maf1 mutants defective in full dephosphorylation display maf1Delta phenotypes and are compromised for both nuclear localization and Pol III association. Repression conditions also promote TFIIIB-TFIIIC interactions in crosslinked chromatin. Taken together, Maf1 appears to integrate environmental conditions and signaling pathways through its phosphorylation state, with stress leading to dephosphorylation, association with Pol III at target loci, alterations in basal factor interactions, and transcriptional repression.

Amino Acid Sequence↗
PubMed2003

Sphingoid bases and their phosphates: transient activation and delayed repression of protein kinase C isoforms and their possible involvement in fumonisin B1 cytotoxicity.

Fumonisin B(1), a potent inhibitor of ceramide synthase, leads to accumulation of sphinganine, and later sphingosine, in vivo and in vitro. Fumonisin B(1) modulates the activity of protein kinase C (PKC), however, which metabolite of disrupted sphingolipid metabolism is involved, has not been ascertained. In the present study, we evaluated the modulation of PKC by sphingolipid bases and their metabolites using exogenous sphingolipid analogues in porcine renal epithelial (LLC-PK(1)) cells. In preliminary studies we found that fumonisin B(1) (1 microM) selectively and transiently activated PKCalpha, whereas fumonisin B(1) concentrations of 1-50 microM at 48 h repressed PKC-alpha, -delta, - epsilon and -zeta isoforms in a concentration-dependent manner. Addition of exogenous sphinganine-1-phosphate (1 microM for 5 min) alone stimulated cytosolic to membrane translocation of PKCalpha. Co-exposure of fumonisin B(1) with N,N-dimethylsphingosine, an inhibitor of sphingosine/sphinganine kinase, prevented the effects of fumonisin B(1) on PKCalpha. Sphinganine, sphingosine, sphingosine-1-phosphate and ceramide (all at 1 microM) added exogenously, did not alter PKCalpha cytosolic to membrane translocation at 5 min. Fumonisin B(1) (10 microM), sphinganine, sphingosine and ceramide (1 microM each) significantly repressed PKC-alpha and -delta isoforms at 48 h, whereas all the exogenously added sphingolipids significantly repressed PKC- epsilon and zeta similar to fumonisin B(1). Co-exposure of myriocin with fumonisin B(1) prevented the delayed inhibitory effects of fumonisin B(1) on PKC isoforms in LLC-PK(1) cells. This study demonstrated that selective and transient activation of PKCalpha may be due to the fumonisin B(1)-induced accumulation of the bioactive sphinganine-1-phosphate, whereas the long-term repression of PKC isoforms may be predominantly due to the accumulation of sphinganine or its metabolite, and to a lesser extent sphingosine or its metabolite in LLC-PK(1) cells. These findings suggest that the direct or indirect modulation of PKC by these sphingolipids is involved at least in part in the action of fumonisin B(1).

Animals↗
PubMed2003

Left-lateralized fMRI activation in the temporal lobe of high repressive women during the identification of sad prosodies.

We investigated with fMRI whether different lateralization types of cortical activation in prosodic tasks are caused by individually different stress-related coping strategies. After healthy women had been classified as high or low repressive they performed four different identification tasks with acoustically presented speech material while being in the MR scanner. The two materials presented in blocks were emotionally irrelevant CV syllables and adjectives with a mix of different prosodic intonations. Sad and happy intonations had to be targeted by two affective identification tasks in the same adjective mixtures. For testing stimulus-material effects the phoneme /a/ had to be identified both in the syllables and the adjectives. This design allowed us to test influences of coping strategies and affective tasks on cortical activation in both hemispheres. Results showed no differences in global cortical lateralization as a function of high or low repressiveness and no global support for either the valence hypothesis or the right-hemisphere hypothesis of emotional processing. However, we observed differences in auditory and speech cortex. In accordance to the construct of repression/sensitization, high repressive women showed larger left, low repressive women larger right hemisphere activation during the identification of sad intonations. Thus, differences in stress-related coping strategies may not lead to general differences in cortical lateralization, but may depend on specific elicitors and task-relevant brain areas. In contrast, the identification of happy intonations led to strong and right-lateralized global cortical activation independent of coping strategies which complies with the right-hemisphere hypothesis of emotional processing. In addition, this may reflect general cognitive and arousal effects of task difficulty as well as auditory cue-specific attentional effects.

Adaptation, Psychological↗
PubMed1995

Can memories of childhood sexual abuse be repressed?

We sought studies which have attempted to test whether memories of childhood sexual abuse can be repressed. Despite our broad search criteria, which excluded only unsystematic anecdotal reports, we found only four applicable studies. We then examined these studies to assess whether the investigators: (1) presented confirmatory evidence that abuse had actually occurred; and (2) demonstrated that their subjects had actually developed amnesia for the abuse. None of the four studies provided both clear confirmation of trauma and adequate documentation of amnesia in their subjects. Thus, present clinical evidence is insufficient to permit the conclusion that individuals can repress memories of childhood sexual abuse. This finding is surprising, since many writers have implied that hundreds of thousands, or even millions of persons harbour such repressed memories. In view of the widespread recent public and scientific interest in the areas of trauma and memory, it is important to investigate further whether memories of sexual abuse can be repressed.

Adolescent↗
PubMed2000

Personality profiles, dissociation, and absorption in women reporting repressed, recovered, or continuous memories of childhood sexual abuse.

Women reporting either repressed, recovered, or continuous memories of childhood sexual abuse or no abuse history completed questionnaires tapping personality traits, absorption (fantasy proneness), dissociation, depression, and posttraumatic stress. Planned contrasts indicated that recovered memory participants scored higher on absorption and dissociation than did those reporting either continuous memories or no abuse history; repressed memory participants scored nonsignificantly higher than did recovered memory participants. On measures of distress, continuous memory participants were indistinguishable from nonabused participants, repressed memory participants scored highest, and recovered memory participants scored midway between continuous and repressed memory participants.

Adolescent↗
PubMed1986

The use of subliminal psychodynamic activation in the study of repression.

Female undergraduates (N = 33) selected for the presence of high sexual guilt were divided into two groups. One group evidenced a high degree of personality development from which it was inferred that they were prone toward (a) the use of repression rather than more primitive defenses and (b) oedipal rather than preoedipal conflict. The second group evidenced a lesser degree of personality development, and hence the above inferences did not apply. The subliminal psychodynamic activation method was used with both groups to investigate the effects on repression of intensifying and diminishing unconscious conflict over sexual wishes. Subjects were exposed to the verbal stimuli "LOVING DADDY IS WRONG" (conflict intensifying), "LOVING DADDY IS OK" (conflict reducing), and "PEOPLE ARE WALKING" (neutral control), each accompanied by a congruent picture both before (in one condition) and after (in another) a recall test of both neutral and sexual material. The conflict-reduction condition did not affect memory of the passages, but the conflict-intensification condition did for the group with the greater degree of personality development, when this condition was presented before the material to be remembered, and for the recall of neutral passages. The special conditions necessary for demonstration of repression are viewed as shedding light on why it has previously been difficult to show evidence of repression in laboratory experiments.

Conflict, Psychological↗
PubMed1987

Repression and the inaccessibility of affective memories.

The fundamental assumption that repression involves an inaccessibility to affective memories has not been directly addressed in empirical research. In the present study we examined three groups of subjects (repressors, low anxious, and high anxious) under six conditions of recall (general, happy, sad, anger, fear, and wonder). Subjects were asked to recall personal experiences from childhood and to rate their current mood and the affective intensity of the memories. The results indicated that repressors recalled significantly fewer negative memories than did low-anxious and high-anxious subjects and, furthermore, that they were substantially older at the time of the earliest negative memory recalled. Compared with low-anxious subjects, repressors also recalled fewer positive affective memories as well. This pattern of findings is consistent with the hypothesis that repression involves an inaccessibility to negative emotional memories and indicates further that repression is associated in some way with the suppression or inhibition of emotional experiences in general. The concept of repression as a process involving limited access to negative affective memories appears to be valid.

Age Factors↗
PubMed1992

Repression at encoding: discrete appraisals of emotional stimuli.

In previous research, the emotions associated with repressors' memorial representations were found to be more discrete than those associated with nonrepressors'. In each of the 3 experiments reported here, repressive discreteness was apparent in repressors' appraisals of emotional stimuli at the time they were encoded. In 1 experiment, Ss appraised individual facial expressions of emotion. Repressors judged the dominant emotions in these faces as no less intense than did nonrepressors, but they appraised the blend of nondominant emotions as less intense than did nonrepressors. In the remaining 2 experiments, Ss appraised crowds of emotional faces as well as crowds of geometric shapes. In both crowd experiments, the repressive discreteness was evident in appraisals of crowds of emotional faces but not in appraisals of crowds of geometric shapes. The repressive discreteness effect did not appear to reflect a general repressor-nonrepressor difference in the appraisal of stimulus features. Rather, the results suggested that repressive discreteness may be constrained to appraisals of emotions.

Adaptation, Psychological↗
PubMed1996

Dispositional and situational determinants of repression.

This research project posits a model of repression that incorporates both repressive personality and repressive social behavior. The 1st parameter of the model specifies the motivation for repressors' distancing of themselves from emotional events. Experiment 1 demonstrates that repressors are hypersensitive--in their cognitive attention--to both negative and positive emotional events. The 2nd parameter of the model specifies the conditions under which repressors distance themselves from emotional events. Experiments 2 and 3 demonstrate that repressors psychologically distance themselves when the situation threatens their self-evaluation and provides opportunity for them to attend to and process self-relevant and non-self-relevant information. This 2-factor model extends the current conceptualization of repression in that it identifies motivation (dispositional emotional sensitivity) and context (situational threats to self-evaluation and distraction availability) for repressors' distancing of themselves from negative and positive emotional events.

Adult↗
PubMed1997

Individual differences in the memory representation of emotional episodes: exploring the cognitive processes in repression.

Two studies investigated the influence of a repressive coping style on the availability and accessibility of emotion memories. In Study 1 participants rated the presence and intensity of emotions in several scenarios and then estimated the frequency of emotions in the scenarios. Repressors did not process the scenarios more superficially. Repressors indicated the presence of unpleasant emotions in the scenarios less frequently, but not less intensely. The frequency differences accounted for most of the repression effects in the latter frequency judgments. In Study 2 participants judged the frequency of emotions twice a day for 2 weeks and then judged the frequency of emotions for the 1st and 2nd week. Repression effects in the frequency judgments did not increase with longer retention intervals. The results indicate that a repressive coping style influences mainly the experience of emotions but not so much the accessibility of emotion memories.

Adaptation, Psychological↗
PubMed1999

Transcriptional repression of the human collagenase-1 (MMP-1) gene in MDA231 breast cancer cells by all-trans-retinoic acid requires distal regions of the promoter.

In the present study, we investigated the mechanisms controlling constitutive transcription of collagenase-1 and its repression by all-trans-retinoic acid (RA) in the highly invasive metastatic and oestrogen-receptor-negative breast cancer cell line MDA231. A combination of in vivo and in vitro experiments that include DNAase I hypersensitivity assays, transient transfection of collagenase-1 promoter constructs, and electrophoretic mobility shift assays implicate several PEA3 sites, binding sites for Ets-related transcription factors, in the constitutive expression of the human collagenase-1 promoter. Transient transfection of promoter constructs linked to the luciferase reporter, along with gel retardation assays, revealed that repression of collagenase-1 transcription by RA is not dependent on the proximal AP-1 site, but, rather, requires sequences located in distal regions of the promoter. Transcriptional analyses and electrophoretic mobility shift assays suggest that the PEA3 site located at -3108 bp facilitates, at least in part, the transcriptional repression of the human collagenase-1 gene in MDA231 cells. We conclude that collagenase-1 repression in MDA231 cells occurs by a novel regulatory pathway that does not depend on the proximal AP-1 site at -73 bp, but does depend on distal regions in the collagenase-1 promoter.

Collagenases↗
PubMed1969

Relaxation of catabolite repression in streptomycin-dependent Escherichia coli.

Acetohydroxy acid synthetase, which is sensitive to catabolite repression in wild-type Escherichia coli B, was relatively resistant to this control in a streptomycin-dependent mutant. The streptomycin-dependent mutant was found to be inducible for beta-galactosidase in the presence of glucose, although repression of beta-galactosidase by glucose occurred under experimental conditions where growth of the streptomycin-dependent mutant was limited. Additional glucose-sensitive enzymes of wild-type E. coli B (citrate synthase, fumarase, aconitase and isocitrate dehydrogenase) were found to be insensitive to the carbon source in streptomycin-dependent mutants: these enzymes were formed by streptomycin-dependent E. coli B in equivalent quantities when either glucose or glycerol was the carbon source. Two enzymes, glucokinase and glucose 6-phosphate dehydrogenase, that are glucose-insensitive in wild-type E. coli B were formed in equivalent quantity on glucose or glycerol in both streptomycin-sensitive and streptomycin-dependent E. coli B. The results indicate a general decrease or relaxation of catabolite repression in the streptomycin-dependent mutant. The yield of streptomycin-dependent cells from glucose was one-third less than that of the streptomycin-sensitive strain. We conclude that the decreased efficiency of glucose utilization in streptomycin-dependent E. coli B is responsible for the relaxation of catabolite repression in this mutant.

Carbonic Anhydrases↗
PubMed1976

Mitochondrial adenosine triphosphatase of the fission yeast, Schizosaccharomyces pombe 972h-. Changes in activity and inhibitor-sensitivity in response to catabolite repression.

1. The specific activity of mitochondrial ATPase (adenosine triphosphatase) in extracts of Schizosaccharomyces pombe decreased 2.5-fold as the glucose concentration in the growth medium decreased from 50mM to 15mM. 2. During the late exponential phase of growth, ATPase activity doubled. 3. Sensitivity to oligomycin and Dio-9 as measured by values for I50(mug of inhibitor/mg of protein giving 50% inhibition) at pH 6.8 increased sixfold and ninefold respectively during the initial decrease in ATPase activity, and this degree of sensitivity was maintained for the remainder of the growth cycle. 4. Increased sensitivity to NN'-dicyclohexylcarbodi-imide, triethyltin and venturicidin was also observed during the early stage of glucose de-repression. 5. Smaller increases in sensitivity to efrapeptin, aurovertin, 7-chloro-4-nitrobenzo-2-oxa-1,3-diaz-le, quercetin and spegazzinine also occurred. 6. The ATPase of glycerol-grown cells was less sensitive to inhibitors than that of glucose-repressed cells; change in values for I50 were not so marked during the growth cycle of cells growing with glycerol. 7. When submitochondrial particles from glycerol-grown cells were tested by passage through Sephadex G-50, a fourfold increase in activity was accompanied by increased inhibitor resistance. 8. Gel filtration of submitochondrial particles from glucose-de-repressed cells gave similar results, whereas loss of ATPase occurred in submitochondrial particles from glucose-repressed cells. 9. It is proposed that alterations in sensitivity to inhibitors at different stages of glucose derepression may be partly controlled by a naturally occuring inhibitor of ATPase. 10. The inhibitors tested may be classififed into two groups on the basis of alterations of sensitivity of the ATPase during physiological modification: (a) oligomycin, Dio-9, NN'-dicyclohexylcarbodi-imide, venturicidin and triethyltin, and (b) efrapeptin, aurovertin, 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole, quercetin and spegazzinine.

Adenosine Triphosphatases↗
PubMed1998

The CreA repressor is the sole DNA-binding protein responsible for carbon catabolite repression of the alcA gene in Aspergillus nidulans via its binding to a couple of specific sites.

Carbon catabolite repression is mediated in Aspergillus nidulans by the negative acting protein CreA. The CreA repressor plays a major role in the control of the expression of the alc regulon, encoding proteins required for the ethanol utilization pathway. It represses directly, at the transcriptional level, the specific transacting gene alcR, the two structural genes alcA and aldA, and other alc genes in all physiological growth conditions. Among the seven putative CreA sites identified in the alcA promoter region, we have determined the CreA functional targets in AlcR constitutive and derepressed genetic backgrounds. Two different divergent CreA sites, of which one overlaps a functional AlcR inverted repeat site, are largely responsible for alcA repression. Totally derepressed alcA expression is achieved when these two CreA sites are disrupted in addition to another single site, which overlaps the functional palindromic induction target. The fact that derepression is always associated with alcA overexpression is consistent with a competition model between AlcR and CreA for their cognate targets in the same region of the alcA promoter. Our results also indicate that the CreA repressor is necessary and sufficient for the total repression of the alcA gene.

Alcohol Dehydrogenase↗
PubMed1994

Dissociated or fabricated? Psychiatric aspects of repressed memory in criminal and civil cases.

During the last decade, clinicians, courts, and researchers have been faced with exceedingly difficult questions involving the crossroads where memory, traumatic memory, dissociation, repression, childhood sexual abuse, and suggestion all meet. In one criminal case, repressed memories served as the basis for a conviction of murder. In approximately 50 civil cases, courts have ruled on the issue of whether repressed memory for childhood sexual abuse may form the basis of a suit against the alleged perpetrators. Rulings that have upheld such use underscore the importance of the reliability of memory retrieval techniques. Hypnosis and other methodologies employed in psychotherapy may be beneficial in working through memories of trauma, but they may also distort memories or alter a subject's evaluation of their veracity. Because of the reconstructive nature of memory, caution must be taken to treat each case on its own merits and avoid global statements essentially proclaiming either that repressed memory is always right or that it is always wrong.

Adolescent↗
PubMed1998

Polycomb group repression is blocked by the Drosophila suppressor of Hairy-wing [su(Hw)] insulator.

The suppressor of Hairy-wing [SU(HW)] binding region disrupts communication between a large number of enhancers and promoters and protects transgenes from chromosomal position effects. These properties classify the SU(HW) binding region as an insulator. While enhancers are blocked in a general manner, protection from repressors appears to be more variable. In these studies, we address whether repression resulting from the Polycomb group genes can be blocked by the SU(HW) binding region. The effects of this binding region on repression established by an Ultrabithorax Polycomb group Response Element were examined. A transposon carrying two reporter genes, the yellow and white genes, was used so that repression and insulation could be assayed simultaneously. We demonstrate that the SU(HW) binding region is effective at preventing Polycomb group repression. These studies suggest that one role of the su(Hw) protein may be to restrict the range of action of repressors, such as the Polycomb group proteins, throughout the euchromatic regions of the genome.

ATP-Binding Cassette Transporters↗
PubMed1974

Regulation of phosphate metabolism in Neurospora crassa: isolation of mutants deficient in ther repressible alkaline phosphatase.

Mutants of Neurospora crassa have been isolated that lack the repressible alkaline phosphatase, but, unlike nuc-1 and nuc-2 mutants, are able to make the repressible acid phosphatase and the repressible phosphate permease under conditions of derepression (phosphate deprivation). The new mutants, called pho-2, map in Linkage Group V, and are unlinked to the putative control mutants, nuc-1, nuc-2-pcon(c), and preg(c). Three of the pho-2 mutants do not make detectable amounts of repressible alkaline phosphatase, but the fourth makes about 1% of the level found in wild type. The small amount of alkaline phosphatase made by this strain appears to be qualitatively similar or identical to the wild-type enzyme, as judged by electrophoretic mobility, heat stability, and titration with specific antibody to the wild-type enzyme. Several revertants of this strain have been examined in the same way, and the alkaline phosphatase of these strains also appears to be qualitatively normal. Reversion events can occur at, or near, the pho-2 locus, but also occur in at least two unlinked sites (suppressor mutations). One suppressor maps very close to nuc-1.

Acid Phosphatase↗