Pantakani, Dasaradha Venkata Krishna

[["dc.bibliographiccitation.firstpage","527"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Wiley Interdisciplinary Reviews - RNA"],["dc.bibliographiccitation.lastpage","535"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Smorag, Lukasz"],["dc.contributor.author","Xu, X."],["dc.contributor.author","Engel, Wolfgang"],["dc.contributor.author","Pantakani, Dasaradha Venkata Krishna"],["dc.date.accessioned","2018-11-07T09:38:38Z"],["dc.date.available","2018-11-07T09:38:38Z"],["dc.date.issued","2014"],["dc.description.abstract","RNA-binding proteins play an important role in the regulation of gene expression by modulating translation and localization of specific messenger RNAs (mRNAs) during early development and gametogenesis. The DAZ (Deleted in Azoospermia) family of proteins, which includes DAZ, DAZL, and BOULE, are germ cell-specific RNA-binding proteins that are implicated in translational regulation of several transcripts. Of particular importance is DAZL, which is present in vertebrates and arose from the duplication of the ancestral BOULE during evolution. Identification of DAZL target mRNAs and characterization of the RNA-binding sequence through in vitro binding assays and crystallographic studies revealed that DAZL binds to GUU triplets in the 3' untranslated region of target mRNAs. Although there is compelling evidence for the role of DAZL in translation stimulation of target mRNAs, recent studies indicate that DAZL can also function in translational repression and transport of specific mRNAs. Furthermore, apart from the well-characterized function of DAZL in gametogenesis, recent data suggest its role in early embryonic development and differentiation of pluripotent stem cells toward functional gametes. In light of the mounting evidence for the role of DAZL in various cellular and developmental processes, we summarize the currently characterized biological functions of DAZL in RNA biology and development. (C) 2014 John Wiley & Sons, Ltd."],["dc.identifier.doi","10.1002/wrna.1228"],["dc.identifier.isi","000337627700006"],["dc.identifier.pmid","24715697"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33108"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1757-7012"],["dc.relation.issn","1757-7004"],["dc.title","The roles of DAZL in RNA biology and development"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","99"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","European Journal of Neurology"],["dc.bibliographiccitation.lastpage","105"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Klimpe, Sven"],["dc.contributor.author","Zibat, Arne"],["dc.contributor.author","Zechner, Ulrich"],["dc.contributor.author","Wellek, B."],["dc.contributor.author","Shoukier, Moneef"],["dc.contributor.author","Sauter, Simone M."],["dc.contributor.author","Pantakani, Dasaradha Venkata Krishna"],["dc.contributor.author","Mannan, Ashraf U."],["dc.date.accessioned","2018-11-07T09:01:10Z"],["dc.date.available","2018-11-07T09:01:10Z"],["dc.date.issued","2011"],["dc.description.abstract","Background: Mutations in the SPG4/SPAST gene are the most common cause for hereditary spastic paraplegia (HSP). The splice-site mutations make a significant contribution to HSP and account for 17.4% of all types of mutations and 30.8% of point mutations in the SPAST gene. However, only few studies with limited molecular approach were conducted to investigate and decipher the role of SPAST splice-site mutations in HSP. Methods: A reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and quantitative allele-specific expression assay were performed. Results: We have characterized the consequence of two novel splice-site mutations (c.1493 + 1G > A and c.1414-1G > A) in the SPAST gene in two different families with pure HSP. The RT-PCR analysis revealed that both spastin mutations are indeed splice-site mutations and cause skipping of exon 12. Furthermore, RT-PCR data suggested that these splice-site mutations may cause leaky splicing. By means of a quantitative allele-specific expression assay, we could confirm that both splice-site mutations cause leaky splicing, as the relative expression of the exon 12-skipped transcript was reduced (21.1 +/- 3.6 compared to expected 50%). Conclusions: Our finding supports a \"threshold-effect-model\" for functional spastin in HSP. A higher level (78.8 +/- 3.9%) of functional spastin than the expected ratio of 50% owing to leaky splicing might cause late age at onset of HSP. Remarkably, we could show that a quantitative allele-specific expression assay is a simple and effective tool to evaluate the role of most types of spastin splice-site mutations in HSP."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft; Institute internal fund"],["dc.identifier.doi","10.1111/j.1468-1331.2010.03079.x"],["dc.identifier.isi","000285356300015"],["dc.identifier.pmid","20491894"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24351"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell Publishing, Inc"],["dc.relation.issn","1351-5101"],["dc.title","Evaluating the effect of spastin splice mutations by quantitative allele-specific expression assay"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","425"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms"],["dc.bibliographiccitation.lastpage","435"],["dc.bibliographiccitation.volume","1829"],["dc.contributor.author","Xu, X."],["dc.contributor.author","Tan, Xiaoying"],["dc.contributor.author","Lin, Qiong"],["dc.contributor.author","Schmidt, Bernhard"],["dc.contributor.author","Engel, Wolfgang"],["dc.contributor.author","Pantakani, Dasaradha Venkata Krishna"],["dc.date.accessioned","2018-11-07T09:25:29Z"],["dc.date.available","2018-11-07T09:25:29Z"],["dc.date.issued","2013"],["dc.description.abstract","Dazl (deleted in azoospermia-like) is an RNA binding protein that is important for germ cell differentiation in vertebrates. In the present study, we report the identification of a novel Dazl isoform (Dazl_Delta 8) that results from alternative splicing of exon8 of mouse Dazl. We observed the expression of Dazl_Delta 8 in various pluripotent cell types, but not in somatic cells. Furthermore, the Dazl_Delta 8 splice variant was expressed along with the full-length isoform of Dazl (Dazl_FL) throughout male germ-cell development and in the ovary. Sub-cellular localization studies of Dazl_Delta 8 revealed a diffused cytoplasmic and large granular pattern, which is similar to the localization patterns of Dazl_FL protein. In contrast to the well documented translation stimulation function in germ cells, overexpression and downregulation studies of Dazl isoforms (Dazl_FL and Dazl_Delta 8) revealed a role for Dazl in the negative translational regulation, of Mvh, a known target of Dazl, as well as Oct3/4 and Sox2 in embryonic stem cells (ESCs). In line with these observations, a luciferase reporter assay with the 3'UTRs of Oct3/4 and Mvh confirmed the translational repressive role of Dazl isoforms in ESCs but not in germ cells derived cell line GC-1. Further, we identified several putative target mRNAs of Dazl_FL and Dazl_Delta 8 in ESCs through RNA-binding immunoprecipitation followed by whole genome transcriptome analysis. Collectively, our results show a translation repression function of Dazl in pluripotent stem cells. (C) 2013 Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.bbagrm.2012.12.010"],["dc.identifier.isi","000318134500001"],["dc.identifier.pmid","23298641"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30075"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","1874-9399"],["dc.title","Mouse Dazl and its novel splice variant functions in translational repression of target mRNAs in embryonic stem cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e22413"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Xu, X."],["dc.contributor.author","Pantakani, Dasaradha Venkata Krishna"],["dc.contributor.author","Luehrig, Sandra"],["dc.contributor.author","Tan, Xiaoying"],["dc.contributor.author","Khromov, Tatjana"],["dc.contributor.author","Nolte, Jessica"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Zechner, Ulrich"],["dc.contributor.author","Engel, Wolfgang"],["dc.date.accessioned","2018-11-07T08:54:13Z"],["dc.date.available","2018-11-07T08:54:13Z"],["dc.date.issued","2011"],["dc.description.abstract","Embryonic stem cells (ESCs) generated from the in-vitro culture of blastocyst stage embryos are known as equivalent to blastocyst inner cell mass (ICM) in-vivo. Though several reports have shown the expression of germ cell/pre-meiotic (GC/PrM) markers in ESCs, their functional relevance for the pluripotency and germ line commitment are largely unknown. In the present study, we used mouse as a model system and systematically analyzed the RNA and protein expression of GC/PrM markers in ESCs and found them to be comparable to the expression of cultured pluripotent cells originated from the germ line. Further, siRNA knockdown experiments have demonstrated the parallel maintenance and independence of pluripotent and GC/PrM networks in ESCs. Through chromatin immunoprecipitation experiments, we observed that pluripotent cells exhibit active chromatin states at GC marker genes and a bivalent chromatin structure at PrM marker genes. Moreover, gene expression analysis during the time course of iPS cells generation revealed that the expression of GC markers precedes pluripotency markers. Collectively, through our observations we hypothesize that the chromatin state and the expression of GC/PrM markers might indicate molecular parallels between in-vivo germ cell specification and pluripotent stem cell generation."],["dc.identifier.doi","10.1371/journal.pone.0022413"],["dc.identifier.isi","000293172900028"],["dc.identifier.pmid","21799849"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8198"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/22620"],["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 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","Stage-Specific Germ-Cell Marker Genes Are Expressed in All Mouse Pluripotent Cell Types and Emerge Early during Induced Pluripotency"],["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","268"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Clinical Genetics"],["dc.bibliographiccitation.lastpage","272"],["dc.bibliographiccitation.volume","73"],["dc.contributor.author","Pantakani, Dasaradha Venkata Krishna"],["dc.contributor.author","Zechner, Ulrich"],["dc.contributor.author","Arygriou, L."],["dc.contributor.author","Pauli, Silke"],["dc.contributor.author","Sauter, Simone M."],["dc.contributor.author","Mannan, Ashraf U."],["dc.date.accessioned","2018-11-07T11:17:25Z"],["dc.date.available","2018-11-07T11:17:25Z"],["dc.date.issued","2008"],["dc.description.abstract","The SPG4 gene is frequently mutated in autosomal dominant form of hereditary spastic paraplegia (HSP). We report that the compound heterozygous sequence variants S44L, a known polymorphism, and c.1687G > A, a novel mutation in SPG4 cause a severe form of HSP in a patient. The family members carrying solely c.1687G > A mutation are asymptomatic for HSP. The reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed that the c.1687G > A mutation is a splice site mutation and causes skipping of the exon 15 of spastin. Furthermore, quantification of RT-PCR products by sequencing and quantification of allele-specific expression by pyrosequencing assay revealed that c.1687G > A is a leaky or hypomorphic splice site mutation. At the protein level, c.1687G > A mutation in SPG4 leads to E563K substitution. In ex vivo study, about 10% of cells expressing E563K mutant spastin showed filamentous expression pattern, suggesting a hypomorphic effect at the protein level. Collectively, our results suggest that S44L in association with c.1687G > A (E563K) drops the functional level of spastin below a threshold limit sufficient to manifest HSP."],["dc.identifier.doi","10.1111/j.1399-0004.2007.00953.x"],["dc.identifier.isi","000252929000012"],["dc.identifier.pmid","18190593"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/54802"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Blackwell Publishing"],["dc.relation.issn","0009-9163"],["dc.title","Compound heterozygosity in the SPG4 gene causes hereditary spastic paraplegia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","613"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Neurochemistry"],["dc.bibliographiccitation.lastpage","624"],["dc.bibliographiccitation.volume","106"],["dc.contributor.author","Pantakani, Dasaradha Venkata Krishna"],["dc.contributor.author","Swapna, Lakshmipuram S."],["dc.contributor.author","Srinivasan, Narayanaswamy"],["dc.contributor.author","Mannan, Ashraf U."],["dc.date.accessioned","2018-11-07T11:13:37Z"],["dc.date.available","2018-11-07T11:13:37Z"],["dc.date.issued","2008"],["dc.description.abstract","Spastin, a member of the ATPases associated with various cellular activities (AAA) family of proteins, is the most frequently mutated in hereditary spastic paraplegia. The defining feature of the AAA proteins is a structurally conserved AAA domain which assembles into an oligomer. By chemical cross-linking and gel filtration chromatography, we show that spastin oligomerizes into a hexamer. Furthermore, to gain a comprehensive overview of the oligomeric structure of spastin, we generated a structural model of the AAA domain of spastin using template structure of VPS4B and p97/VCP. The generated model of spastin provided us with a framework to classify the identified missense mutations in the AAA domain from hereditary spastic paraplegia patients into different structural/functional groups. Finally, through co-localization studies in mammalian cells, we show that E442Q mutant spastin acts in a dominant negative fashion and causes redistribution of both wild-type spastin monomer and spastin interacting protein, RTN1 into filamentous microtubule bundles."],["dc.identifier.doi","10.1111/j.1471-4159.2008.05414.x"],["dc.identifier.isi","000257708000011"],["dc.identifier.pmid","18410514"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/53940"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Blackwell Publishing"],["dc.relation.issn","0022-3042"],["dc.title","Spastin oligomerizes into a hexamer and the mutant spastin (E442Q) redistribute the wild-type spastin into filamentous microtubule"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","6008"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.lastpage","11"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Xu, Xingbo"],["dc.contributor.author","Smorag, Lukasz"],["dc.contributor.author","Nakamura, Toshinobu"],["dc.contributor.author","Kimura, Tohru"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Fitzner, Antje"],["dc.contributor.author","Tan, Xiaoying"],["dc.contributor.author","Linke, Matthias"],["dc.contributor.author","Zechner, Ulrich"],["dc.contributor.author","Engel, Wolfgang"],["dc.contributor.author","Pantakani, D.V. Krishna"],["dc.date.accessioned","2018-11-07T10:03:46Z"],["dc.date.available","2018-11-07T10:03:46Z"],["dc.date.issued","2015"],["dc.description.abstract","Reprogramming of mouse somatic cells into induced pluripotent stem cells (iPSCs) often generates partially reprogrammed iPSCs (pre-iPSCs), low-grade chimera forming iPSCs (lg-iPSCs) and fully reprogrammed, high-grade chimera production competent iPSCs (hg-iPSCs). Lg-iPSC transcriptome analysis revealed misregulated Dlk1-Dio3 cluster gene expression and subsequently the imprinting defect at the Dlk1-Dio3 locus. Here, we show that germ-cell marker Dppa3 is present only in lg-iPSCs and hg-iPSCs, and that induction with exogenous Dppa3 enhances reprogramming kinetics, generating all hg-iPSCs, similar to vitamin C (Vc). Conversely, Dppa3-null fibroblasts show reprogramming block at pre-iPSCs state and Dlk1-Dio3 imprinting defect. At the molecular level, we show that Dppa3 is associated with Dlk1-Dio3 locus and identify that Dppa3 maintains imprinting by antagonizing Dnmt3a binding. Our results further show molecular parallels between Dppa3 and Vc in Dlk1-Dio3 imprinting maintenance and suggest that early activation of Dppa3 is one of the cascades through which Vc facilitates the generation of fully reprogrammed iPSCs."],["dc.identifier.doi","10.1038/ncomms7008"],["dc.identifier.isi","000348812400009"],["dc.identifier.pmid","25613421"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11863"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/38545"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/130"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","Najko"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C05: Bedeutung von zellulären Immunreaktionen für das kardiale Remodeling und die Therapie der Herzinsuffizienz durch Stammzelltransplantation"],["dc.relation.issn","2041-1723"],["dc.relation.workinggroup","RG Dressel"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Dppa3 expression is critical for generation of fully reprogrammed iPS cells and maintenance of Dlk1-Dio3 imprinting"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1045"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Stem Cell Research"],["dc.bibliographiccitation.lastpage","1059"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Tan, Xiaoying"],["dc.contributor.author","Xu, X."],["dc.contributor.author","Elkenani, Manar"],["dc.contributor.author","Smorag, Lukasz"],["dc.contributor.author","Zechner, Ulrich"],["dc.contributor.author","Nolte, Jessica"],["dc.contributor.author","Engel, Wolfgang"],["dc.contributor.author","Pantakani, Dasaradha Venkata Krishna"],["dc.date.accessioned","2018-11-07T09:17:54Z"],["dc.date.available","2018-11-07T09:17:54Z"],["dc.date.issued","2013"],["dc.description.abstract","Pluripotency is maintained by both known and unknown transcriptional regulatory networks. In the present study, we have identified Zfp819, a KRAB-zinc finger protein, as a novel pluripotency-related factor and characterized its role in pluripotent stem cells. We show that Zfp819 is expressed highly in various types of pluripotent stem cells but not in their differentiated counterparts. We identified the presence of non-canonical nuclear localization signals in particular zinc finger motifs and identified them as responsible for the nuclear localization of Zfp819. Analysis of the Zfp819 promoter region revealed the presence of a transcriptionally active chromatin signature. Moreover, we confirmed the binding of pluripotency-related factors, Oct4, Sox2, and Nanog to the distal promoter region of Zfp819, indicating that the expression of this gene is regulated by a pluripotency transcription factor network. We found that the expression of endogenous retroviral elements (ERVs) such as Intracisternal A Particle (IAP) retrotransposons, Long Interspersed Nuclear Elements (LINE1), and Short Interspersed Nuclear Elements (SINE B1) is significantly upregulated in Zfp819-knockdown (Zfp819_KD) cells. In line with the activation of ERVs, we observed the occurrence of spontaneous DNA damage in Zfp819_KD cells. Furthermore, we tested whether Zfp819 can interact with KAP1, a KRAB-associated protein with a transcriptional repression function, and found the interaction between these two proteins in both in vitro and in vivo experiments. The challenging of Zfp819_KD cells with DNA damaging agent revealed that these cells are inefficient in repairing the damaged DNA, as cells showed presence of gamma H2A.X foci for a prolonged time. Collectively, our study identified Zfp819 as a novel pluripotency-related factor and unveiled its function in genomic integrity maintenance mechanisms of mouse embryonic stem cells. (C) 2013 Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.scr.2013.07.006"],["dc.identifier.isi","327905300008"],["dc.identifier.pmid","23954693"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/28283"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","1876-7753"],["dc.relation.issn","1873-5061"],["dc.title","Zfp819, a novel KRAB-zinc finger protein, interacts with KAP1 and functions in genomic integrity maintenance of mouse embryonic stem cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","166"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","MHR Basic science of reproductive medicine"],["dc.bibliographiccitation.lastpage","174"],["dc.bibliographiccitation.volume","17"],["dc.contributor.author","Khromov, Tatjana"],["dc.contributor.author","Pantakani, Dasaradha Venkata Krishna"],["dc.contributor.author","Nolte, Jessica"],["dc.contributor.author","Wolf, Marieke"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Engel, Wolfgang"],["dc.contributor.author","Zechner, Ulrich"],["dc.date.accessioned","2018-11-07T08:58:57Z"],["dc.date.available","2018-11-07T08:58:57Z"],["dc.date.issued","2011"],["dc.description.abstract","We previously reported the generation of multipotent adult germline stem cells (maGSCs) from spermatogonial stem cells (SSCs) isolated from adult mouse testis. In a later study, we substantiated the pluripotency of maGSCs by demonstrating their close similarity to pluripotent male embryonic stem cells (ESCs) at the epigenetic level of global and gene-specific DNA methylation. Here, we extended the comparative epigenetic analysis of maGSCs and male ESCs by investigating the second main epigenetic modification in mammals, i.e. global and gene-specific modifications of histones (H3K4 trimethylation, H3K9 acetylation, H3K9 trimethylation and H3K27 trimethylation). Using immunofluorescence staining, flow cytometry and western blot analysis, we show that maGSCs are very similar to male ESCs with regard to global levels and nuclear distribution patterns of these modifications. Chromatin immunoprecipitation real-time PCR analysis of these modifications at the gene-specific level further revealed modification patterns of the pluripotency marker genes Oct4, Sox2 and Nanog in maGSCs that are nearly identical to those of male ESCs. These genes were enriched for activating histone modifications including H3K4me3 and H3K9ac and depleted of repressive histone modifications including H3K27me3 and H3K9me3. In addition, Hoxa11, a key regulator of early embryonic development showed the ESC-typical bivalent chromatin conformation with enrichment of both the activating H3K4me3 and the repressive H3K27me3 modification also in maGSCs. Collectively, our results demonstrate that maGSCs also closely resemble ESCs with regard to their chromatin state and further evidence their pluripotent nature."],["dc.identifier.doi","10.1093/molehr/gaq085"],["dc.identifier.isi","000287257000003"],["dc.identifier.pmid","20935159"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23771"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","1360-9947"],["dc.title","Global and gene-specific histone modification profiles of mouse multipotent adult germline stem cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","7453"],["dc.bibliographiccitation.issue","21"],["dc.bibliographiccitation.journal","Molecules"],["dc.bibliographiccitation.volume","27"],["dc.contributor.affiliation","Shahid, Sidra; 1Institute for Clinical Chemistry, University Medical Centre Goettingen, 37075 Goettingen, Germany"],["dc.contributor.affiliation","Pantakani, Marlena; 1Institute for Clinical Chemistry, University Medical Centre Goettingen, 37075 Goettingen, Germany"],["dc.contributor.affiliation","Binder, Lutz; 1Institute for Clinical Chemistry, University Medical Centre Goettingen, 37075 Goettingen, Germany"],["dc.contributor.affiliation","Fischer, Andreas; 1Institute for Clinical Chemistry, University Medical Centre Goettingen, 37075 Goettingen, Germany"],["dc.contributor.affiliation","Pantakani, Krishna; 1Institute for Clinical Chemistry, University Medical Centre Goettingen, 37075 Goettingen, Germany"],["dc.contributor.affiliation","Asif, Abdul R.; 1Institute for Clinical Chemistry, University Medical Centre Goettingen, 37075 Goettingen, Germany"],["dc.contributor.author","Shahid, Sidra"],["dc.contributor.author","Pantakani, Marlena"],["dc.contributor.author","Binder, Lutz"],["dc.contributor.author","Fischer, Andreas"],["dc.contributor.author","Pantakani, Krishna"],["dc.contributor.author","Asif, Abdul R."],["dc.date.accessioned","2022-12-07T15:55:02Z"],["dc.date.available","2022-12-07T15:55:02Z"],["dc.date.issued","2022-11-02"],["dc.date.updated","2022-12-07T14:41:11Z"],["dc.description.abstract","NF-κB signaling is a key regulator of inflammation and atherosclerosis. NF-κB cooperates with bromodomain-containing protein 4 (BRD4), a transcriptional and epigenetic regulator, in endothelial inflammation. This study aimed to investigate whether BRD4 inhibition would prevent the proinflammatory response towards TNF-α in endothelial cells. We used TNF-α treatment of human umbilical cord-derived vascular endothelial cells to create an in vitro inflammatory model system. Two small molecule inhibitors of BRD4—namely, RVX208 (Apabetalone), which is in clinical trials for the treatment of atherosclerosis, and JQ1—were used to analyze the effect of BRD4 inhibition on endothelial inflammation and barrier integrity. BRD4 inhibition reduced the expression of proinflammatory markers such as SELE, VCAM-I, and IL6 in endothelial cells and prevented TNF-α-induced endothelial tight junction hyperpermeability. Endothelial inflammation was associated with increased expression of the heparin-binding growth factor midkine. BRD4 inhibition reduced midkine expression and normalized endothelial permeability upon TNF-α treatment. In conclusion, we identified that TNF-α increased midkine expression and compromised tight junction integrity in endothelial cells, which was preventable by pharmacological BRD4 inhibition."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft (DFG)"],["dc.description.sponsorship","Volkswagen Stiftung"],["dc.description.sponsorship","Göttingen University"],["dc.identifier.doi","10.3390/molecules27217453"],["dc.identifier.pii","molecules27217453"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/118485"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-621"],["dc.relation.eissn","1420-3049"],["dc.rights","CC BY 4.0"],["dc.title","Small Molecule BRD4 Inhibitors Apabetalone and JQ1 Rescues Endothelial Cells Dysfunction, Protects Monolayer Integrity and Reduces Midkine Expression"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]