Staab, Julia F.

[["dc.bibliographiccitation.firstpage","A143"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Psychosomatic Medicine"],["dc.bibliographiccitation.lastpage","A144"],["dc.bibliographiccitation.volume","78"],["dc.contributor.author","Staab, Julia"],["dc.contributor.author","Herrmann-Lingen, Christoph"],["dc.contributor.author","Meyer, Thomas"],["dc.date.accessioned","2018-11-07T10:15:43Z"],["dc.date.available","2018-11-07T10:15:43Z"],["dc.date.issued","2016"],["dc.identifier.isi","000373949800470"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40870"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.publisher.place","Philadelphia"],["dc.relation.conference","74th Annual Meeting of the American-Psychosomatic-Society"],["dc.relation.eventlocation","Denver, CO"],["dc.relation.issn","1534-7796"],["dc.relation.issn","0033-3174"],["dc.title","SITE-DIRECTED MUTAGENESIS OF STAT1 TRANSCRIPTION FACTOR IN THE STUDY OF INTERFERON-INDUCED DEPRESSION"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","11193"],["dc.bibliographiccitation.issue","21"],["dc.bibliographiccitation.journal","International Journal of Environmental Research and Public Health"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Veiz, Elisabeth"],["dc.contributor.author","Kieslich, Susann-Kristin"],["dc.contributor.author","Staab, Julia"],["dc.contributor.author","Czesnik, Dirk"],["dc.contributor.author","Herrmann-Lingen, Christoph"],["dc.contributor.author","Meyer, Thomas"],["dc.date.accessioned","2021-12-01T09:22:50Z"],["dc.date.available","2021-12-01T09:22:50Z"],["dc.date.issued","2021"],["dc.description.abstract","This paper presents data from a transcutaneous vagus nerve stimulation experiment that point towards a blunted cardiac baroreceptor sensitivity (cBRS) in young males compared to females during electrical stimulation of the forearm and a rhythmic breathing task. Continuous electrocardiography, impedance cardiography and continuous blood-pressure recordings were assessed in a sex-matched cohort of twenty young healthy subjects. Electrical stimulation of the median nerve was conducted by using a threshold-tracking method combined with two rhythmic breathing tasks (0.1 and 0.2 Hz) before, during and after active or sham transcutaneous vagus nerve stimulation. Autonomic and hemodynamic parameters were calculated, and differences were analyzed by using linear mixed models and post hoc F-tests. None of the autonomic and hemodynamic parameters differed between the sham and active conditions. However, compared to females, male participants had an overall lower total cBRS independent of stimulation condition during nerve stimulation (females: 14.96 ± 5.67 ms/mmHg, males: 11.89 ± 3.24 ms/mmHg, p = 0.031) and rhythmic breathing at 0.2 Hz (females: 21.49 ± 8.47 ms/mmHg, males: 15.12 ± 5.70 ms/mmHg, p = 0.004). Whereas vagus nerve stimulation at the left inner tragus did not affect the efferent vagal control of the heart, we found similar patterns of baroreceptor sensitivity activation over the stimulation period in both sexes, which, however, significantly differed in their magnitude, with females showing an overall higher cBRS."],["dc.description.abstract","This paper presents data from a transcutaneous vagus nerve stimulation experiment that point towards a blunted cardiac baroreceptor sensitivity (cBRS) in young males compared to females during electrical stimulation of the forearm and a rhythmic breathing task. Continuous electrocardiography, impedance cardiography and continuous blood-pressure recordings were assessed in a sex-matched cohort of twenty young healthy subjects. Electrical stimulation of the median nerve was conducted by using a threshold-tracking method combined with two rhythmic breathing tasks (0.1 and 0.2 Hz) before, during and after active or sham transcutaneous vagus nerve stimulation. Autonomic and hemodynamic parameters were calculated, and differences were analyzed by using linear mixed models and post hoc F-tests. None of the autonomic and hemodynamic parameters differed between the sham and active conditions. However, compared to females, male participants had an overall lower total cBRS independent of stimulation condition during nerve stimulation (females: 14.96 ± 5.67 ms/mmHg, males: 11.89 ± 3.24 ms/mmHg, p = 0.031) and rhythmic breathing at 0.2 Hz (females: 21.49 ± 8.47 ms/mmHg, males: 15.12 ± 5.70 ms/mmHg, p = 0.004). Whereas vagus nerve stimulation at the left inner tragus did not affect the efferent vagal control of the heart, we found similar patterns of baroreceptor sensitivity activation over the stimulation period in both sexes, which, however, significantly differed in their magnitude, with females showing an overall higher cBRS."],["dc.identifier.doi","10.3390/ijerph182111193"],["dc.identifier.pii","ijerph182111193"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/94492"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-478"],["dc.publisher","MDPI"],["dc.relation.eissn","1660-4601"],["dc.rights","Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)."],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Men Show Reduced Cardiac Baroreceptor Sensitivity during Modestly Painful Electrical Stimulation of the Forearm: Exploratory Results from a Sham-Controlled Crossover Vagus Nerve Stimulation Study"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e69903"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Staab, Julia"],["dc.contributor.author","Herrmann-Lingen, Christoph"],["dc.contributor.author","Meyer, Thomas"],["dc.date.accessioned","2018-11-07T09:22:18Z"],["dc.date.available","2018-11-07T09:22:18Z"],["dc.date.issued","2013"],["dc.description.abstract","A transition from a parallel to an antiparallel dimer configuration of the transcription factor signal transducer and activator of transcription 1 (STAT1) is required for interferon (IFN)-mediated signal transduction. However, the precise molecular mechanisms linking conformational changes to target gene activation by STAT1 are still largely unknown. In the present study, we have characterized, in more detail than before, two disease-associated point mutants with amino acid substitutions at both sites of the dimer interface (F172W and T385A). First, we confirmed that IFN gamma-stimulation of transfected cells led to enhanced tyrosine phosphorylation of mutant STAT1 as compared to the wild-type protein, which consequently resulted in its prolonged nuclear accumulation. Using an in vitro dephosphorylation assay, we demonstrated that, in contrast to wild-type STAT1 and similar to the F172W mutant, also T385A resisted enzymatic inactivation by the nuclear phosphatase Tc45. Transcriptional activation of IFN gamma-driven endogenous target genes differed between wild-type and mutant STAT1. While expression of genes containing a single classical gamma-activated site (GAS), such as irf1, gpb1, and mig1, was virtually unaffected by the presence of either of two amino acid exchanges, induction of the cxcl10 and mcp1 gene was significantly enhanced. The latter two genes both contain an additional TTC/GAA binding motif separated by 10 bp from the palindromic GAS sequence. The transcriptional superiority of the mutants on these genes was reflected by their increased binding affinity to DNA fragments containing the identified \"one-and-a-half-GAS\" motif. In summary, our data demonstrate that two clinically relevant interface mutants of STAT1 exhibit gene-specific effects and point to the rather complex role of the assumed conformational shift between two different dimer configurations for efficient transcriptional regulation."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft"],["dc.identifier.doi","10.1371/journal.pone.0069903"],["dc.identifier.isi","000322838900107"],["dc.identifier.pmid","23922848"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9174"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29312"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY-NC 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/3.0"],["dc.title","Clinically Relevant Dimer Interface Mutants of STAT1 Transcription Factor Exhibit Differential Gene Expression"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","596"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Molecular Immunology"],["dc.bibliographiccitation.lastpage","606"],["dc.bibliographiccitation.volume","67"],["dc.contributor.author","Staab, Julia"],["dc.contributor.author","Riebeling, Theresa"],["dc.contributor.author","Koch, Verena"],["dc.contributor.author","Herrmann-Lingen, Christoph"],["dc.contributor.author","Meyer, Thomas"],["dc.date.accessioned","2018-11-07T09:51:03Z"],["dc.date.available","2018-11-07T09:51:03Z"],["dc.date.issued","2015"],["dc.description.abstract","Defective cooperative DNA binding of STAT1 (signal transducer and activator of transcription 1) transcription factor has impact on interferon-gamma(IFN gamma)-regulated transcriptional responses. In this study, we generated N-terminal gain-of-function mutants of this protein which exhibited hyperactive cooperativity and assessed their functional consequences on gene expression. Our data show that four negatively charged, surface-exposed amino acid residues in the N-terminal domain dimer are engaged in the disassembly of tyrosine-phosphorylated tetrameric complexes on DNA and prevent the occurrence of higher-order STAT1 oligomers on low-affinity DNA binding sites. Owing to their improved tetramer stability, the N-terminal mutants showed relaxed sequence requirements for the binding to DNA as compared to the wild-type protein. Similarly to a STAT1 mutant with impaired tetramerization, the N-terminal gain-of-function mutants showed elevated tyrosine-phosphorylation levels and prolonged nuclear accumulation upon stimulation of cells with IFN gamma. However, in contrast to the global impairment of IFN gamma signalling in tetramerization-deficient mutants, the transcriptional consequences of the N-terminal gain-of-function mutants are rather distinct and affect gene expression locally in a promoter-specific manner. Thus, we conclude that the STAT1 N-domain acts as a double-edged sword: while one interface is crucial for the formation of tetrameric complexes on IFN gamma-regulated promoters, the opposite interface harbours an inhibitory mechanism that limits the accumulation of higher-order oligomers simply by disrupting cooperative DNA binding. (C) 2015 Published by Elsevier Ltd."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft (DFG) [1816]; DFG"],["dc.identifier.doi","10.1016/j.molimm.2015.07.015"],["dc.identifier.isi","000361922400045"],["dc.identifier.pmid","26275341"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35836"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","0161-5890"],["dc.title","The two interfaces of the STAT1 N-terminus exhibit opposite functions in IFN gamma-regulated gene expression"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","631"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Biochemical Genetics"],["dc.bibliographiccitation.lastpage","648"],["dc.bibliographiccitation.volume","58"],["dc.contributor.author","Meyer, Thomas"],["dc.contributor.author","Rothe, Isabel"],["dc.contributor.author","Staab, Julia"],["dc.contributor.author","Deter, Hans-Christian"],["dc.contributor.author","Fangauf, Stella V."],["dc.contributor.author","Hamacher, Stefanie"],["dc.contributor.author","Hellmich, Martin"],["dc.contributor.author","Jünger, Jana"],["dc.contributor.author","Ladwig, Karl-Heinz"],["dc.contributor.author","Michal, Matthias"],["dc.contributor.author","Petrowski, Katja"],["dc.contributor.author","Ronel, Joram"],["dc.contributor.author","Söllner, Wolfgang"],["dc.contributor.author","Weber, Cora"],["dc.contributor.author","de Zwaan, Martina"],["dc.contributor.author","Williams, Redford B."],["dc.contributor.author","Albus, Christian"],["dc.contributor.author","Herrmann-Lingen, Christoph"],["dc.date.accessioned","2020-12-10T14:11:22Z"],["dc.date.available","2020-12-10T14:11:22Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1007/s10528-020-09967-w"],["dc.identifier.eissn","1573-4927"],["dc.identifier.issn","0006-2928"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/71058"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Length Polymorphisms in the Angiotensin I-Converting Enzyme Gene and the Serotonin-Transporter-Linked Polymorphic Region Constitute a Risk Haplotype for Depression in Patients with Coronary Artery Disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Neuroimmunomodulation"],["dc.bibliographiccitation.lastpage","10"],["dc.contributor.author","Veiz, Elisabeth"],["dc.contributor.author","Kieslich, Susann-Kristin"],["dc.contributor.author","Czesnik, Dirk"],["dc.contributor.author","Herrmann‐Lingen, Christoph"],["dc.contributor.author","Meyer, Thomas J."],["dc.contributor.author","Staab, Julia"],["dc.date.accessioned","2022-06-01T09:39:38Z"],["dc.date.available","2022-06-01T09:39:38Z"],["dc.date.issued","2022"],["dc.description.abstract","The vagus nerve constitutes the main component of the parasympathetic nervous system and plays an important role in the regulation of neuro-immune responses. Invasive stimulation of the vagus nerve produces anti-inflammatory effects; however, data on humoral immune responses of transcutaneous vagus nerve stimulation (tVNS) are rare. Therefore, the present study investigated changes in serum cytokine concentrations of interleukin-1β (IL-1β), IL-6, IL-8, and tumor necrosis factor α (TNFα) following a short-term, non-invasive stimulation of the vagus nerve. <b><i>Methods:</i></b> Whole blood samples were collected before and after a short-lived application of active tVNS at the inner tragus as well as sham stimulation of the earlobe. Cytokine serum concentrations were determined in two healthy cohorts of younger (<i>n</i> = 20) and older participants (<i>n</i> = 19). Differences between active and sham conditions were analyzed using linear mixed models and post hoc <i>F</i> tests after applying Yeo-Johnson power transformations. This trial was part of a larger study registered on ClinicalTrials.gov (NCT05007743). <b><i>Results:</i></b> In the young cohort, IL-6 and IL-1β concentrations were significantly increased after active stimulation, whereas they were slightly decreased after sham stimulation (IL-6: <i>p</i> = 0.012; IL-1β: <i>p</i> = 0.012). Likewise, in the older cohort, IL-1β and IL-8 concentrations were significantly elevated after active stimulation and reduced after sham application (IL-8: <i>p</i> = 0.007; IL-1β: <i>p</i> = 0.001). In contrast, circulating TNFα concentrations did not change significantly in either group. <b><i>Conclusion:</i></b> Our results show that active tVNS led to an immediate increase in the serum concentrations of certain pro-inflammatory cytokines such as IL-1β, IL-6, and/or IL-8 in two independent cohorts of healthy study participants."],["dc.identifier.doi","10.1159/000524646"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/108524"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-572"],["dc.relation.eissn","1423-0216"],["dc.relation.issn","1021-7401"],["dc.relation.orgunit","Abteilung Klinische Psychologie und Psychotherapie"],["dc.relation.orgunit","Klinik für Neurologie"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.title","Increased Concentrations of Circulating Interleukins following Non-Invasive Vagus Nerve Stimulation: Results from a Randomized, Sham-Controlled, Crossover Study in Healthy Subjects"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Psychosomatic Medicine"],["dc.bibliographiccitation.volume","75"],["dc.contributor.author","Staab, Julia"],["dc.contributor.author","Koch, Verena"],["dc.contributor.author","Herrmann-Lingen, Christoph"],["dc.contributor.author","Meyer, Thomas"],["dc.date.accessioned","2018-11-07T09:26:09Z"],["dc.date.available","2018-11-07T09:26:09Z"],["dc.date.issued","2013"],["dc.format.extent","A81"],["dc.identifier.isi","000330467400256"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30233"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.publisher.place","Philadelphia"],["dc.relation.conference","71st Annual Scientific Meeting of the American-Psychosomatic-Society"],["dc.relation.eventlocation","Miami, FL"],["dc.relation.issn","1534-7796"],["dc.relation.issn","0033-3174"],["dc.title","HIGH-AFFINITY DNA-BINDING MUTANTS OF THE STAT1 TRANSCRIPTION FACTOR USED AS TOOLS IN THE STUDY OF INTERFERON-INDUCED DEPRESSION"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","European Journal of Cardio-Thoracic Surgery"],["dc.contributor.author","Sadlonova, Monika"],["dc.contributor.author","Nagel, Jonas"],["dc.contributor.author","Becker, Svenja"],["dc.contributor.author","Neumann, Sophie"],["dc.contributor.author","Staab, Julia"],["dc.contributor.author","Meyer, Thomas"],["dc.contributor.author","Celano, Christopher M"],["dc.contributor.author","Amonoo, Hermioni L"],["dc.contributor.author","Fangauf, Stella V"],["dc.contributor.author","Herrmann-Lingen, Christoph"],["dc.contributor.author","Friedrich, Martin"],["dc.date.accessioned","2022-04-01T10:02:49Z"],["dc.date.available","2022-04-01T10:02:49Z"],["dc.date.issued","2022"],["dc.description.abstract","Abstract OBJECTIVES Patients undergoing coronary artery bypass graft (CABG) surgery are exposed to multiple treatment-related stressors, which can impact coping and health-related quality of life (HRQoL). The objective of this trial was to analyse the feasibility and preliminary efficacy of a multi-component intervention that combines psychological support and reduction of hospital-specific stressors on HRQoL, length of hospital and intensive care unit stay, self-efficacy, and plasma interleukin (IL)-6 and -8 levels in CABG patients. METHODS This three-arm, randomized controlled, single-centre pilot trial assessed the Intervention for CABG to Optimize Patient Experience in 88 patients undergoing elective CABG. Standard medical care (SMC, n = 29) was compared with 2 intervention groups: (i) psychological interventions to optimize treatment expectations (IA group, n = 30) and (ii) multi-component intervention (IB group, n = 29) with psychological interventions plus an additional treatment package (light therapy, noise reduction, music, and if desired, 360° images delivered via virtual reality). RESULTS The implementation of psychological interventions in routine medical treatment was feasible (91.5% of participants completed all intervention sessions). Both interventions were associated with significantly shorter hospital stay compared to SMC (IA/IB 9.8/9.3 days vs SMC 12.5 days). Self-efficacy expectations at post-surgery were significantly higher compared to SMC both in the IA group (P = 0.011) and marginally in the IB group (P = 0.051). However, there were no treatment effects of the interventions on HRQoL and plasma levels of IL-6 or IL-8 after CABG. CONCLUSIONS A perioperative multi-component intervention may lead to shorter hospital stay and higher self-efficacy after CABG. Further studies are needed to determine its impact on HRQoL and inflammation. CLINICAL TRIAL REGISTRATION NUMBER Ethical approval (# 21/2/18) for the study was obtained from the Research Ethics Committee of the University of Göttingen Medical Center, and the trial was registered in the German Clinical Trials Register (DRKS00015309, https://www.drks.de/drks_web/setLocale_EN.do)."],["dc.identifier.doi","10.1093/ejcts/ezac041"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/106014"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-530"],["dc.relation.eissn","1873-734X"],["dc.relation.issn","1010-7940"],["dc.title","Feasibility and preliminary efficacy of perioperative interventions in patients undergoing coronary artery bypass grafting: the randomized controlled I-COPE trial"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Psychosomatic Medicine"],["dc.bibliographiccitation.volume","76"],["dc.contributor.author","Meyer, Thomas"],["dc.contributor.author","Staab, Julia"],["dc.contributor.author","Huentelmann, Bettina"],["dc.contributor.author","Herrmann-Lingen, Christoph"],["dc.date.accessioned","2018-11-07T09:41:43Z"],["dc.date.available","2018-11-07T09:41:43Z"],["dc.date.issued","2014"],["dc.format.extent","A131"],["dc.identifier.isi","000334235100546"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33793"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.publisher.place","Philadelphia"],["dc.relation.conference","72nd Annual Meeting of the American-Psychosomatic-Society"],["dc.relation.eventlocation","San Francisco, CA"],["dc.relation.issn","1534-7796"],["dc.relation.issn","0033-3174"],["dc.title","A MOLECULAR APPROACH TO THE STUDY OF DEPRESSION: MODULATING DNA BINDING OF STAT1 TRANSCRIPTION FACTOR BY SITE-DIRECTED MUTAGENESIS"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e97633"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Huentelmann, Bettina"],["dc.contributor.author","Staab, Julia"],["dc.contributor.author","Herrmann-Lingen, Christoph"],["dc.contributor.author","Meyer, Thomas"],["dc.date.accessioned","2018-11-07T09:40:02Z"],["dc.date.available","2018-11-07T09:40:02Z"],["dc.date.issued","2014"],["dc.description.abstract","Binding to specific palindromic sequences termed gamma-activated sites (GAS) is a hallmark of gene activation by members of the STAT (signal transducer and activator of transcription) family of cytokine-inducible transcription factors. However, the precise molecular mechanisms involved in the signal-dependent finding of target genes by STAT dimers have not yet been very well studied. In this study, we have characterized a sequence motif in the STAT1 linker domain which is highly conserved among the seven human STAT proteins and includes surface-exposed residues in close proximity to the bound DNA. Using site-directed mutagenesis, we have demonstrated that a lysine residue in position 567 of the full-length molecule is required for GAS recognition. The substitution of alanine for this residue completely abolished both binding to high-affinity GAS elements and transcriptional activation of endogenous target genes in cells stimulated with interferon-c (IFN gamma), while the time course of transient nuclear accumulation and tyrosine phosphorylation were virtually unchanged. In contrast, two glutamic acid residues (E559 and E563) on each monomer are important for the dissociation of dimeric STAT1 from DNA and, when mutated to alanine, result in elevated levels of tyrosine-phosphorylated STAT1 as well as prolonged IFN gamma-stimulated nuclear accumulation. In conclusion, our data indicate that the kinetics of signal-dependent GAS binding is determined by an array of glutamic acid residues located at the interior surface of the STAT1 dimer. These negatively charged residues appear to align the long axis of the STAT1 dimer in a position perpendicular to the DNA, thereby facilitating the interaction between lysine 567 and the phosphodiester backbone of a bound GAS element, which is a prerequisite for transient gene induction."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [TM1648]"],["dc.identifier.doi","10.1371/journal.pone.0097633"],["dc.identifier.isi","000336730600044"],["dc.identifier.pmid","24847715"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10126"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33422"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","A Conserved Motif in the Linker Domain of STAT1 Transcription Factor Is Required for Both Recognition and Release from High-Affinity DNA-Binding Sites"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]