Pantakani, Dasaradha Venkata Krishna

[["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","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","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"]]