Johnsen, Steven Arthur

[["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Cell Death & Disease"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Kosinsky, Robyn Laura"],["dc.contributor.author","Helms, Marlena"],["dc.contributor.author","Zerche, Maria"],["dc.contributor.author","Wohn, Luisa"],["dc.contributor.author","Dyas, Anna"],["dc.contributor.author","Prokakis, Evangelos"],["dc.contributor.author","Kazerouni, Zahra Basir"],["dc.contributor.author","Bedi, Upasana"],["dc.contributor.author","Wegwitz, Florian"],["dc.contributor.author","Johnsen, Steven A."],["dc.date.accessioned","2020-12-10T18:09:43Z"],["dc.date.available","2020-12-10T18:09:43Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1038/s41419-019-2141-9"],["dc.identifier.eissn","2041-4889"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17081"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/73737"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","USP22-dependent HSP90AB1 expression promotes resistance to HSP90 inhibition in mammary and colorectal cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","13"],["dc.bibliographiccitation.journal","Epigenetics & Chromatin"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Prenzel, Tanja"],["dc.contributor.author","Kramer, Frank"],["dc.contributor.author","Bedi, Upasana"],["dc.contributor.author","Nagarajan, Sankari"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Johnsen, Steven Arthur"],["dc.date.accessioned","2018-11-07T09:07:07Z"],["dc.date.available","2018-11-07T09:07:07Z"],["dc.date.issued","2012"],["dc.description.abstract","Background: In conjunction with posttranslational chromatin modifications, proper arrangement of higher order chromatin structure appears to be important for controlling transcription in the nucleus. Recent genome-wide studies have shown that the Estrogen Receptor-alpha (ER alpha), encoded by the ESR1 gene, nucleates tissue-specific long-range chromosomal interactions in collaboration with the cohesin complex. Furthermore, the Mediator complex not only regulates ERa activity, but also interacts with the cohesin complex to facilitate long-range chromosomal interactions. However, whether the cohesin and Mediator complexes function together to contribute to estrogen-regulated gene transcription remains unknown. Results: In this study we show that depletion of the cohesin subunit SMC3 or the Mediator subunit MED12 significantly impairs the ER alpha-regulated transcriptome. Surprisingly, SMC3 depletion appears to elicit this effect indirectly by rapidly decreasing ESR1 transcription and ER alpha protein levels. Moreover, we provide evidence that both SMC3 and MED12 colocalize on the ESR1 gene and are mutually required for their own occupancy as well as for RNAPII occupancy across the ESR1 gene. Finally, we show that extended proteasome inhibition decreases the mRNA expression of cohesin subunits which accompanies a decrease in ESR1 mRNA and ERa protein levels as well as estrogen-regulated transcription. Conclusions: These results identify the ESR1 gene as a cohesin/Mediator-dependent gene and indicate that this regulation may potentially be exploited for the treatment of estrogen-dependent breast cancer."],["dc.identifier.doi","10.1186/1756-8935-5-13"],["dc.identifier.isi","000310834100001"],["dc.identifier.pmid","22913342"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12877"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/25716"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1756-8935"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","Cohesin is required for expression of the estrogen receptor-alpha (ESR1) gene"],["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.journal","Oncogene"],["dc.contributor.author","Prokakis, Evangelos"],["dc.contributor.author","Dyas, Anna"],["dc.contributor.author","Grün, Regina"],["dc.contributor.author","Fritzsche, Sonja"],["dc.contributor.author","Bedi, Upasana"],["dc.contributor.author","Kazerouni, Zahra B."],["dc.contributor.author","Kosinsky, Robyn L."],["dc.contributor.author","Johnsen, Steven A."],["dc.contributor.author","Wegwitz, Florian"],["dc.date.accessioned","2021-06-01T09:41:38Z"],["dc.date.available","2021-06-01T09:41:38Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract The Ubiquitin-Specific Protease 22 (USP22) is a deubiquitinating subunit of the mammalian SAGA transcriptional co-activating complex. USP22 was identified as a member of the so-called “death-from-cancer” signature predicting therapy failure in cancer patients. However, the importance and functional role of USP22 in different types and subtypes of cancer remain largely unknown. In the present study, we leveraged human cell lines and genetic mouse models to investigate the role of USP22 in HER2-driven breast cancer (HER2 + -BC) and demonstrate for the first time that USP22 is required for the tumorigenic properties in murine and human HER2 + -BC models. To get insight into the underlying mechanisms, we performed transcriptome-wide gene expression analyses and identified the Unfolded Protein Response (UPR) as a pathway deregulated upon USP22 loss. The UPR is normally induced upon extrinsic or intrinsic stresses that can promote cell survival and recovery if shortly activated or programmed cell death if activated for an extended period. Strikingly, we found that USP22 actively suppresses UPR induction in HER2 + -BC cells by stabilizing the major endoplasmic reticulum (ER) chaperone HSPA5. Consistently, loss of USP22 renders tumor cells more sensitive to apoptosis and significantly increases the efficiency of therapies targeting the ER folding capacity. Together, our data suggest that therapeutic strategies targeting USP22 activity may sensitize tumor cells to UPR induction and could provide a novel, effective approach to treat HER2 + -BC."],["dc.identifier.doi","10.1038/s41388-021-01814-5"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/84989"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation.eissn","1476-5594"],["dc.relation.issn","0950-9232"],["dc.title","USP22 promotes HER2-driven mammary carcinoma aggressiveness by suppressing the unfolded protein response"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2016"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","2029"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Bedi, Upasana"],["dc.contributor.author","Mishra, Vivek Kumar"],["dc.contributor.author","Wasilewski, David"],["dc.contributor.author","Johnsen, Steven A."],["dc.contributor.author","Scheel, Christina H."],["dc.date.accessioned","2021-11-22T14:31:31Z"],["dc.date.available","2021-11-22T14:31:31Z"],["dc.date.issued","2014-04-30"],["dc.description.abstract","Tumor metastasis is the major cause of mortality and morbidity in most solid cancers. A growing body of evidence suggests that the epithelial-to-mesenchymal transition (EMT) plays a central role during tumor metastasis and frequently imparts a stem cell-like phenotype and therapeutic resistance to tumor cells. The induction of EMT is accompanied by a dynamic reprogramming of the epigenome involving changes in DNA methylation and several post-translational histone modifications. These changes in turn promote the expression of mesenchymal genes or repress those associated with an epithelial phenotype. Importantly, in order for metastatic colonization and the formation of macrometastases to occur, tumor cells frequently undergo a reversal of EMT referred to as the mesenchymal-to-epithelial transition (MET). Thus, a high degree of epigenetic plasticity is required in order to induce and reverse EMT during tumor progression. In this review, we describe various epigenetic regulatory mechanisms employed by tumor cells during EMT and elaborate on the importance of the histone code in controlling both the expression and activity of EMT-associated transcription factors. We propose that a more thorough understanding of the epigenetic mechanisms controlling EMT may provide new opportunities which may be harnessed for improved and individualized cancer therapy based on defined molecular mechanisms."],["dc.identifier.doi","10.18632/oncotarget.1875"],["dc.identifier.fs","610581"],["dc.identifier.isi","000336965800002"],["dc.identifier.pmid","24840099"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12959"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/93384"],["dc.language","eng"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Impact Journals Llc"],["dc.relation.issn","1949-2553"],["dc.rights.access","openAccess"],["dc.subject","Epigenetics; Chromatin; Cancer; Epithelial-to-mesenchymal transition; Metastasis"],["dc.subject.mesh","Animals"],["dc.subject.mesh","Epigenesis, Genetic"],["dc.subject.mesh","Epithelial-Mesenchymal Transition"],["dc.subject.mesh","Gene Expression Regulation, Neoplastic"],["dc.subject.mesh","Humans"],["dc.subject.mesh","Neoplasms"],["dc.title","Epigenetic plasticity: A central regulator of epithelial-to-mesenchymal transition in cancer"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3130"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Nucleic Acids Research"],["dc.bibliographiccitation.lastpage","3145"],["dc.bibliographiccitation.volume","45"],["dc.contributor.author","Nagarajan, Sankari"],["dc.contributor.author","Bedi, Upasana"],["dc.contributor.author","Budida, Anusha"],["dc.contributor.author","Hamdan, Feda H."],["dc.contributor.author","Mishra, Vivek Kumar"],["dc.contributor.author","Najafova, Zeynab"],["dc.contributor.author","Xie, Wanhua"],["dc.contributor.author","Alawi, Malik"],["dc.contributor.author","Indenbirken, Daniela"],["dc.contributor.author","Knapp, Stefan"],["dc.contributor.author","Chiang, Cheng-Ming"],["dc.contributor.author","Grundhoff, Adam"],["dc.contributor.author","Kari, Vijayalakshmi"],["dc.contributor.author","Scheel, Christina H."],["dc.contributor.author","Wegwitz, Florian"],["dc.contributor.author","Johnsen, Steven A."],["dc.date.accessioned","2018-11-07T10:25:04Z"],["dc.date.available","2018-11-07T10:25:04Z"],["dc.date.issued","2017"],["dc.description.abstract","Bromodomain-containing protein 4 (BRD4) is a member of the bromo-and extraterminal (BET) domain-containing family of epigenetic readers which is under intensive investigation as a target for anti-tumor therapy. BRD4 plays a central role in promoting the expression of select subsets of genes including many driven by oncogenic transcription factors and signaling pathways. However, the role of BRD4 and the effects of BET inhibitors in non-transformed cells remain mostly unclear. We demonstrate that BRD4 is required for the maintenance of a basal epithelial phenotype by regulating the expression of epithelial-specific genes including TP63 and Grainy Head-like transcription factor-3 (GRHL3) in non-transformed basal-like mammary epithelial cells. Moreover, BRD4 occupancy correlates with enhancer activity and enhancer RNA (eRNA) transcription. Motif analyses of cell context-specific BRD4-enriched regions predicted the involvement of FOXOtranscription factors. Consistently, activation of FOXO1 function via inhibition of EGFR-AKT signaling promoted the expression of TP63 and GRHL3. Moreover, activation of Src kinase signaling and FOXO1 inhibition decreased the expression of FOXO/BRD4 target genes. Together, our findings support a function for BRD4 in promoting basal mammary cell epithelial differentiation, at least in part, by regulating FOXO factor function on enhancers to activate TP63 and GRHL3 expression."],["dc.identifier.doi","10.1093/nar/gkw1276"],["dc.identifier.isi","000398376200026"],["dc.identifier.pmid","27980063"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14764"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42778"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","1362-4962"],["dc.relation.issn","0305-1048"],["dc.rights","CC BY-NC 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/4.0"],["dc.title","BRD4 promotes p63 and GRHL3 expression downstream of FOXO in mammary epithelial cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","459"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Cell Reports"],["dc.bibliographiccitation.lastpage","468"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Nagarajan, Sankari"],["dc.contributor.author","Hossan, Tareq"],["dc.contributor.author","Alawi, Malik"],["dc.contributor.author","Najafova, Zeynab"],["dc.contributor.author","Indenbirken, Daniela"],["dc.contributor.author","Bedi, Upasana"],["dc.contributor.author","Taipaleenmaeki, Hanna"],["dc.contributor.author","Ben-Batalla, Isabel"],["dc.contributor.author","Scheller, Marina"],["dc.contributor.author","Loges, Sonja"],["dc.contributor.author","Knapp, Stefan"],["dc.contributor.author","Hesse, Eric"],["dc.contributor.author","Chiang, Cheng-Ming"],["dc.contributor.author","Grundhoff, Adam"],["dc.contributor.author","Johnsen, Steven A."],["dc.date.accessioned","2018-11-07T09:37:31Z"],["dc.date.available","2018-11-07T09:37:31Z"],["dc.date.issued","2014"],["dc.description.abstract","The estrogen receptor alpha (ER alpha) controls cell proliferation and tumorigenesis by recruiting various cofactors to estrogen response elements (EREs) to control gene transcription. A deeper understanding of these transcriptional mechanisms may uncover therapeutic targets for ER alpha-dependent cancers. We show that BRD4 regulates ER alpha-induced gene expression by affecting elongation-associated phosphorylation of RNA polymerase II (RNAPII) and histone H2B monoubiquitination. Consistently, BRD4 activity is required for proliferation of ER+ breast and endometrial cancer cells and uterine growth in mice. Genome-wide studies revealed an enrichment of BRD4 on transcriptional start sites of active genes and a requirement of BRD4 for H2B monoubiquitination in the transcribed region of estrogen-responsive genes. Importantly, we demonstrate that BRD4 occupancy on distal EREs enriched for H3K27ac is required for recruitment and elongation of RNAPII on EREs and the production of ER alpha-dependent enhancer RNAs. These results uncover BRD4 as a central regulator of ER alpha function and potential therapeutic target."],["dc.identifier.doi","10.1016/j.celrep.2014.06.016"],["dc.identifier.isi","000341569800016"],["dc.identifier.pmid","25017071"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11372"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32862"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Cell Press"],["dc.relation.issn","2211-1247"],["dc.rights","CC BY-NC-ND 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/3.0"],["dc.title","Bromodomain Protein BRD4 Is Required for Estrogen Receptor-Dependent Enhancer Activation and Gene Transcription"],["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","465"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Oncogene"],["dc.bibliographiccitation.lastpage","473"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Bedi, Upasana"],["dc.contributor.author","Scheel, Andreas Hans"],["dc.contributor.author","Hennion, Magali"],["dc.contributor.author","Begus-Nahrmann, Yvonne"],["dc.contributor.author","Rueschoff, Josef"],["dc.contributor.author","Johnsen, Steven A."],["dc.date.accessioned","2018-11-07T10:02:02Z"],["dc.date.available","2018-11-07T10:02:02Z"],["dc.date.issued","2015"],["dc.description.abstract","The estrogen receptor alpha (ER alpha) is the central transcriptional regulator of ductal mammary epithelial lineage specification and is an important prognostic marker in human breast cancer. Although antiestrogen therapies are initially highly effective at treating ER alpha-positive tumors, a large number of tumors progress to a refractory, more poorly differentiated phenotype accompanied by reduced survival. A better understanding of the molecular mechanisms involved in the progression from estrogen-dependent to hormone-resistant breast cancer may uncover new targets for treatment and the discovery of new predictive markers. Recent studies have uncovered an important role for transcriptional elongation and chromatin modifications in controlling ER alpha activity and estrogen responsiveness. The human Suppressor of Ty Homologue-6 (SUPT6H) is a histone chaperone that links transcriptional elongation to changes in chromatin structure. We show that SUPT6H is required for estrogen-regulated transcription and the maintenance of chromatin structure in breast cancer cells, possibly in part through interaction with RNF40 and regulation of histone H2B monoubiquitination (H2Bub1). Moreover, we demonstrate that SUPT6H protein levels decrease with malignancy in breast cancer. Consistently, SUPT6H, similar to H2Bub1, is required for cellular differentiation and suppression of the repressive histone mark H3K27me3 on lineage-specific genes. Together, these data identify SUPT6H as a new epigenetic regulator of ER alpha activity and cellular differentiation."],["dc.identifier.doi","10.1038/onc.2013.558"],["dc.identifier.isi","000348451300007"],["dc.identifier.pmid","24441044"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/38146"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1476-5594"],["dc.relation.issn","0950-9232"],["dc.title","SUPT6H controls estrogen receptor activity and cellular differentiation by multiple epigenomic mechanisms"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","127"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nucleic Acids Research"],["dc.bibliographiccitation.lastpage","141"],["dc.bibliographiccitation.volume","45"],["dc.contributor.author","Najafova, Zeynab"],["dc.contributor.author","Tirado-Magallanes, Roberto"],["dc.contributor.author","Subramaniam, Malayannan"],["dc.contributor.author","Hossan, Tareq"],["dc.contributor.author","Schmidt, Geske"],["dc.contributor.author","Nagarajan, Sankari"],["dc.contributor.author","Baumgart, Simon J."],["dc.contributor.author","Mishra, Vivek Kumar"],["dc.contributor.author","Bedi, Upasana"],["dc.contributor.author","Hesse, Eric"],["dc.contributor.author","Knapp, Stefan"],["dc.contributor.author","Hawse, John R."],["dc.contributor.author","Johnsen, Steven A."],["dc.date.accessioned","2018-11-07T10:28:57Z"],["dc.date.available","2018-11-07T10:28:57Z"],["dc.date.issued","2017"],["dc.description.abstract","Proper temporal epigenetic regulation of gene expression is essential for cell fate determination and tissue development. The Bromodomain-containing Protein-4 (BRD4) was previously shown to control the transcription of defined subsets of genes in various cell systems. In this study we examined the role of BRD4 in promoting lineage-specific gene expression and show that BRD4 is essential for osteoblast differentiation. Genome-wide analyses demonstrate that BRD4 is recruited to the transcriptional start site of differentiation-induced genes. Unexpectedly, while promoter-proximal BRD4 occupancy correlated with gene expression, genes which displayed moderate expression and promoter-proximal BRD4 occupancy were most highly regulated and sensitive to BRD4 inhibition. Therefore, we examined distal BRD4 occupancy and uncovered a specific co-localization of BRD4 with the transcription factors C/EBPb, TEAD1, FOSL2 and JUND at putative osteoblast-specific enhancers. These findings reveal the intricacies of lineage specification and provide new insight into the context-dependent functions of BRD4."],["dc.identifier.doi","10.1093/nar/gkw826"],["dc.identifier.isi","000396575100016"],["dc.identifier.pmid","27651452"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14409"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43538"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","1362-4962"],["dc.relation.issn","0305-1048"],["dc.rights","CC BY-NC 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/4.0"],["dc.title","BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire"],["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"]]