Johnsen, Steven Arthur

[["dc.bibliographiccitation.journal","Cancer Research"],["dc.bibliographiccitation.volume","76"],["dc.contributor.author","Mishra, Vivek Kumar"],["dc.contributor.author","Kari, Vijayalakshmi"],["dc.contributor.author","Subramaniam, Malayannan"],["dc.contributor.author","Baumgart, Simon J."],["dc.contributor.author","Nagarajan, Sankari"],["dc.contributor.author","Wegwitz, Florian"],["dc.contributor.author","Spelsberg, Thomas C."],["dc.contributor.author","Hawse, John R."],["dc.contributor.author","Johnsen, Steven A."],["dc.date.accessioned","2018-11-07T10:19:22Z"],["dc.date.available","2018-11-07T10:19:22Z"],["dc.date.issued","2016"],["dc.identifier.doi","10.1158/1538-7445.CHROMEPI15-A03"],["dc.identifier.isi","000368930800003"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41642"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Cancer Research"],["dc.publisher.place","Philadelphia"],["dc.relation.conference","American-Association-for-Cancer-Research (AACR) Special Conference on Chromatin and Epigenetics in Cancer"],["dc.relation.eventlocation","Atlanta, GA"],["dc.relation.issn","1538-7445"],["dc.relation.issn","0008-5472"],["dc.title","Kruppel-like Transcription Factor-10 (KLF10) suppresses the TGF beta-induced epithelial-to-mesenchymal transition"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1024"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Gastroenterology"],["dc.bibliographiccitation.lastpage","U502"],["dc.bibliographiccitation.volume","148"],["dc.contributor.author","Chen, Nai-Ming"],["dc.contributor.author","Singh, Garima"],["dc.contributor.author","Koenig, Alexander O."],["dc.contributor.author","Liou, Geou-Yarh"],["dc.contributor.author","Storz, Peter"],["dc.contributor.author","Zhang, J."],["dc.contributor.author","Regul, Lisanne"],["dc.contributor.author","Nagarajan, Sankari"],["dc.contributor.author","Kuehnemuth, Benjamin"],["dc.contributor.author","Johnsen, Steven A."],["dc.contributor.author","Hebrok, Matthias"],["dc.contributor.author","Siveke, Jens T."],["dc.contributor.author","Billadeau, Daniel D."],["dc.contributor.author","Ellenrieder, Volker"],["dc.contributor.author","Heßmann, Elisabeth"],["dc.date.accessioned","2018-11-07T09:57:58Z"],["dc.date.available","2018-11-07T09:57:58Z"],["dc.date.issued","2015"],["dc.description.abstract","BACKGROUND & AIMS: Oncogenic mutations in KRAS contribute to the development of pancreatic ductal adenocarcinoma, but are not sufficient to initiate carcinogenesis. Secondary events, such as inflammation-induced signaling via the epidermal growth factor receptor (EGFR) and expression of the SOX9 gene, are required for tumor formation. Herein we sought to identify the mechanisms that link EGFR signaling with activation of SOX9 during acinar-ductal metaplasia, a transdifferentiation process that precedes pancreatic carcinogenesis. METHODS: We analyzed pancreatic tissues from KrasG12D; pdx1-Cre and KrasG12D; NFATc1D/D; pdx1-Cre mice after intraperitoneal administration of caerulein, vs cyclosporin A or dimethyl sulfoxide (controls). Induction of EGFR signaling and its effects on the expression of Nuclear factor of activated T cells c1 (NFATc1) or SOX9 were investigated by quantitative reverse-transcription polymerase chain reaction, immunoblot, and immunohistochemical analyses of mouse and human tissues and acinar cell explants. Interactions between NFATc1 and partner proteins and effects on DNA binding or chromatin modifications were studied using co-immunoprecipitation and chromatin immunoprecipitation assays in acinar cell explants and mouse tissue. RESULTS: EGFR activation induced expression of NFATc1 in metaplastic areas from patients with chronic pancreatitis and in pancreatic tissue from KrasG12D mice. EGFR signaling also promoted formation of a complex between NFATc1 and C-JUN in dedifferentiating mouse acinar cells, leading to activation of Sox9 transcription and induction of acinar-ductal metaplasia. Pharmacologic inhibition of NFATc1 or disruption of the Nfatc1 gene inhibited EGFR-mediated induction of Sox9 transcription and blocked acinar-ductal transdifferentiation and pancreatic cancer initiation in mice. CONCLUSIONS: EGFR signaling induces expression of NFATc1 and Sox9, leading to acinar cell transdifferentiation and initiation of pancreatic cancer. Strategies designed to disrupt this pathway might be developed to prevent pancreatic cancer initiation in high-risk patients with chronic pancreatitis."],["dc.identifier.doi","10.1053/j.gastro.2015.01.033"],["dc.identifier.isi","000353335700033"],["dc.identifier.pmid","25623042"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37276"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","W B Saunders Co-elsevier Inc"],["dc.relation.issn","1528-0012"],["dc.relation.issn","0016-5085"],["dc.title","NFATc1 Links EGFR Signaling to Induction of Sox9 Transcription and Acinar-Ductal Transdifferentiation in the Pancreas"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","7722"],["dc.bibliographiccitation.issue","13"],["dc.bibliographiccitation.journal","Nucleic Acids Research"],["dc.bibliographiccitation.lastpage","7735"],["dc.bibliographiccitation.volume","45"],["dc.contributor.author","Baumgart, Simon J."],["dc.contributor.author","Najafova, Zeynab"],["dc.contributor.author","Hossan, Tareq"],["dc.contributor.author","Xie, Wanhua"],["dc.contributor.author","Nagarajan, Sankari"],["dc.contributor.author","Kari, Vijayalakshmi"],["dc.contributor.author","Ditzel, Nicholas"],["dc.contributor.author","Kassem, Moustapha"],["dc.contributor.author","Johnsen, Steven A."],["dc.date.accessioned","2020-12-10T18:19:34Z"],["dc.date.available","2020-12-10T18:19:34Z"],["dc.date.issued","2017"],["dc.identifier.doi","10.1093/nar/gkx377"],["dc.identifier.eissn","1362-4962"],["dc.identifier.issn","0305-1048"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/75295"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","CHD1 regulates cell fate determination by activation of differentiation-induced genes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","7305"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","7317"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Nagarajan, Sankari"],["dc.contributor.author","Benito-Garagorri, Eva"],["dc.contributor.author","Fischer, Andre"],["dc.contributor.author","Johnsen, Steven A."],["dc.date.accessioned","2017-09-07T11:52:22Z"],["dc.date.available","2017-09-07T11:52:22Z"],["dc.date.issued","2015"],["dc.description.abstract","Hormone-dependent gene expression requires dynamic and coordinated epigenetic changes. Estrogen receptor-positive (ER+) breast cancer is particularly dependent upon extensive chromatin remodeling and changes in histone modifications for the induction of hormone-responsive gene expression. Our previous studies established an important role of bromodomain-containing protein-4 (BRD4) in promoting estrogen-regulated transcription and proliferation of ER+ breast cancer cells. Here, we investigated the association between genome-wide occupancy of histone H4 acetylation at lysine 12 (H4K12ac) and BRD4 in the context of estrogen-induced transcription. Similar to BRD4, we observed that H4K12ac occupancy increases near the transcription start sites (TSS) of estrogen-induced genes as well as at distal ERα binding sites in an estrogen-dependent manner. Interestingly, H4K12ac occupancy highly correlates with BRD4 binding and enhancer RNA production on ERα-positive enhancers. Consistent with an importance in estrogen-induced gene transcription, H4K12ac occupancy globally increased in ER-positive cells relative to ER-negative cells and these levels were further increased by estrogen treatment in an ERα-dependent manner. Together, these findings reveal a strong correlation between H4K12ac and BRD4 occupancy with estrogen-dependent gene transcription and further suggest that modulators of H4K12ac and BRD4 may serve as new therapeutic targets for hormone-dependent cancers."],["dc.identifier.doi","10.18632/oncotarget.3439"],["dc.identifier.gro","3144913"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13612"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2590"],["dc.language.iso","en"],["dc.notes.intern","Crossref Import"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.issn","1949-2553"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","H4K12ac is regulated by estrogen receptor-alpha and is associated with BRD4 function and inducible transcription"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1369"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Stem Cells"],["dc.bibliographiccitation.lastpage","1376"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Hossan, Tareq"],["dc.contributor.author","Nagarajan, Sankari"],["dc.contributor.author","Baumgart, Simon J."],["dc.contributor.author","Xie, Wanhua"],["dc.contributor.author","Magallanes, Roberto Tirado"],["dc.contributor.author","Hernandez, Celine"],["dc.contributor.author","Chiaroni, Pierre-Marie"],["dc.contributor.author","Indenbirken, Daniela"],["dc.contributor.author","Spitzner, Melanie"],["dc.contributor.author","Thomas-Chollier, Morgane"],["dc.contributor.author","Grade, Marian"],["dc.contributor.author","Thieffry, Denis"],["dc.contributor.author","Grundhoff, Adam"],["dc.contributor.author","Wegwitz, Florian"],["dc.contributor.author","Johnsen, Steven A."],["dc.date.accessioned","2018-11-07T10:15:04Z"],["dc.date.available","2018-11-07T10:15:04Z"],["dc.date.issued","2016"],["dc.description.abstract","Cellular differentiation is accompanied by dramatic changes in chromatin structure which direct the activation of lineage-specific transcriptional programs. Structure-specific recognition protein-1 (SSRP1) is a histone chaperone which is important for chromatin-associated processes such as transcription, DNA replication and repair. Since the function of SSRP1 during cell differentiation remains unclear, we investigated its potential role in controlling lineage determination. Depletion of SSRP1 in human mesenchymal stem cells elicited lineage-specific effects by increasing expression of adipocyte-specific genes and decreasing the expression of osteoblast-specific genes. Consistent with a role in controlling lineage specification, transcriptome-wide RNA-sequencing following SSRP1 depletion and the induction of osteoblast differentiation revealed a specific decrease in the expression of genes involved in biological processes related to osteoblast differentiation. Importantly, we observed a specific downregulation of target genes of the canonical Wnt signaling pathway, which was accompanied by decreased nuclear localization of active beta-catenin. Together our data uncover a previously unknown role for SSRP1 in promoting the activation of the Wnt signaling pathway activity during cellular differentiation."],["dc.identifier.doi","10.1002/stem.2287"],["dc.identifier.isi","000375896900021"],["dc.identifier.pmid","27146025"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40740"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1549-4918"],["dc.relation.issn","1066-5099"],["dc.title","Histone Chaperone SSRP1 is Essential for Wnt Signaling Pathway Activity During Osteoblast Differentiation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3572"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Journal of Clinical Investigation"],["dc.bibliographiccitation.lastpage","3584"],["dc.bibliographiccitation.volume","125"],["dc.contributor.author","Benito-Garagorri, Eva"],["dc.contributor.author","Urbanke, Hendrik"],["dc.contributor.author","Ramachandran, Binu"],["dc.contributor.author","Barth, Jonas"],["dc.contributor.author","Haider, Rashi"],["dc.contributor.author","Awasthi, Ankit"],["dc.contributor.author","Jain, Gaurav"],["dc.contributor.author","Capece, Vincenzo"],["dc.contributor.author","Burkhardt, Susanne"],["dc.contributor.author","Navarro-Sala, Magdalena"],["dc.contributor.author","Nagarajan, Sankari"],["dc.contributor.author","Schuetz, Anna-Lena"],["dc.contributor.author","Johnsen, Steven A."],["dc.contributor.author","Bonn, Stefan"],["dc.contributor.author","Luehrmann, Reinhard"],["dc.contributor.author","Dean, Camin"],["dc.contributor.author","Fischer, Andre"],["dc.date.accessioned","2017-09-07T11:43:34Z"],["dc.date.available","2017-09-07T11:43:34Z"],["dc.date.issued","2015"],["dc.description.abstract","Aging and increased amyloid burden are major risk factors for cognitive diseases such as Alzheimer's disease (AD). Effective therapies for these diseases are lacking. Here, we evaluated mouse models of age-associated memory impairment and amyloid deposition to study transcriptome and cell type-specific epigenome plasticity in the brain and peripheral organs. We determined that aging and amyloid pathology are associated with inflammation and impaired synaptic function in the hippocampal CA1 region as the result of epigenetic-dependent alterations in gene expression. In both amyloid and aging models, inflammation was associated with increased gene expression linked to a subset of transcription factors, while plasticity gene deregulation was differentially mediated. Amyloid pathology impaired histone acetylation and decreased expression of plasticity genes, while aging altered H4K12 acetylation-linked differential splicing at the intron-exon junction in neurons, but not nonneuronal cells. Furthermore, oral administration of the clinically approved histone deacetylase inhibitor vorinostat not only restored spatial memory, but also exerted antiinflammatory action and reinstated epigenetic balance and transcriptional homeostasis at the level of gene expression and exon usage. This study provides a systems-level investigation of transcriptome plasticity in the hippocampal CA1 region in aging and AD models and suggests that histone deacetylase inhibitors should be further explored as a cost-effective therapeutic strategy against age-associated cognitive decline."],["dc.identifier.doi","10.1172/JCI79942"],["dc.identifier.gro","3141833"],["dc.identifier.isi","000362303600031"],["dc.identifier.pmid","26280576"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1579"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1558-8238"],["dc.relation.issn","0021-9738"],["dc.title","HDAC inhibitor-dependent transcriptome and memory reinstatement in cognitive decline models"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["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.artnumber","32"],["dc.bibliographiccitation.journal","Genome Biology"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Xie, Wanhua"],["dc.contributor.author","Nagarajan, Sankari"],["dc.contributor.author","Baumgart, Simon J."],["dc.contributor.author","Kosinsky, Robyn Laura"],["dc.contributor.author","Najafova, Zeynab"],["dc.contributor.author","Kari, Vijayalakshmi"],["dc.contributor.author","Hennion, Magali"],["dc.contributor.author","Indenbirken, Daniela"],["dc.contributor.author","Bonn, Stefan"],["dc.contributor.author","Grundhoff, Adam"],["dc.contributor.author","Wegwitz, Florian"],["dc.contributor.author","Mansouri, Ahmed"],["dc.contributor.author","Johnsen, Steven A."],["dc.date.accessioned","2018-11-07T10:27:18Z"],["dc.date.available","2018-11-07T10:27:18Z"],["dc.date.issued","2017"],["dc.description.abstract","Background: Monoubiquitination of H2B (H2Bub1) is a largely enigmatic histone modification that has been linked to transcriptional elongation. Because of this association, it has been commonly assumed that H2Bub1 is an exclusively positively acting histone modification and that increased H2Bub1 occupancy correlates with increased gene expression. In contrast, depletion of the H2B ubiquitin ligases RNF20 or RNF40 alters the expression of only a subset of genes. Results: Using conditional Rnf40 knockout mouse embryo fibroblasts, we show that genes occupied by low to moderate amounts of H2Bub1 are selectively regulated in response to Rnf40 deletion, whereas genes marked by high levels of H2Bub1 are mostly unaffected by Rnf40 loss. Furthermore, we find that decreased expression of RNF40-dependent genes is highly associated with widespread narrowing of H3K4me3 peaks. H2Bub1 promotes the broadening of H3K4me3 to increase transcriptional elongation, which together lead to increased tissue- specific gene transcription. Notably, genes upregulated following Rnf40 deletion, including Foxl2, are enriched for H3K27me3, which is decreased following Rnf40 deletion due to decreased expression of the Ezh2 gene. As a consequence, increased expression of some RNF40-\"suppressed\" genes is associated with enhancer activation via FOXL2. Conclusion: Together these findings reveal the complexity and context-dependency whereby one histone modification can have divergent effects on gene transcription. Furthermore, we show that these effects are dependent upon the activity of other epigenetic regulatory proteins and histone modifications."],["dc.identifier.doi","10.1186/s13059-017-1159-5"],["dc.identifier.isi","000394828000003"],["dc.identifier.pmid","28209164"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14250"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43221"],["dc.notes.intern","Merged from goescholar"],["dc.notes.intern","In goescholar not merged with http://resolver.sub.uni-goettingen.de/purl?gs-1/14993 but duplicate"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1474-760X"],["dc.rights","CC BY 4.0"],["dc.rights.access","openAccess"],["dc.rights.holder","The Author(s)."],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","RNF40 regulates gene expression in an epigenetic context-dependent manner"],["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","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","2387"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Cancer Research"],["dc.bibliographiccitation.lastpage","2400"],["dc.bibliographiccitation.volume","77"],["dc.contributor.author","Mishra, Vivek Kumar"],["dc.contributor.author","Subramaniam, Malayannan"],["dc.contributor.author","Kari, Vijayalakshmi"],["dc.contributor.author","Pitel, Kevin S."],["dc.contributor.author","Baumgart, Simon J."],["dc.contributor.author","Naylor, Ryan M."],["dc.contributor.author","Nagarajan, Sankari"],["dc.contributor.author","Wegwitz, Florian"],["dc.contributor.author","Ellenrieder, Volker"],["dc.contributor.author","Hawse, John R."],["dc.contributor.author","Johnsen, Steven A."],["dc.date.accessioned","2020-12-10T18:37:44Z"],["dc.date.available","2020-12-10T18:37:44Z"],["dc.date.issued","2017"],["dc.description.abstract","TGFb-SMAD signaling exerts a contextual effect that suppresses malignant growth early in epithelial tumorigenesis but promotes metastasis at later stages. Longstanding challenges in resolving this functional dichotomy may uncover new strategies to treat advanced carcinomas. The Kruppel-like transcription factor, KLF10, is a pivotal effector of TGF beta/SMAD signaling that mediates antiproliferative effects of TGF beta. In this study, we show how KLF10 opposes the prometastatic effects of TGFb by limiting its ability to induce epithelial-to-mesenchymal transition (EMT). KLF10 depletion accentuated induction of EMT as assessed by multiple metrics. KLF10 occupied GC-rich sequences in the promoter region of the EMT-promoting transcription factor SLUG/SNAI2, repressing its transcription by recruiting HDAC1 and licensing the removal of activating histone acetylation marks. In clinical specimens of lung adenocarcinoma, low KLF10 expression associated with decreased patient survival, consistent with a pivotal role for KLF10 in distinguishing the antiproliferative versus prometastatic functions of TGFb. Our results establish that KLF10 functions to suppress TGFb-induced EMT, establishing a molecular basis for the dichotomy of TGFb function during tumor progression. (C) 2017 AACR."],["dc.identifier.doi","10.1158/0008-5472.CAN-16-2589"],["dc.identifier.eissn","1538-7445"],["dc.identifier.isi","000400270100021"],["dc.identifier.issn","0008-5472"],["dc.identifier.pmid","28249899"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77078"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Amer Assoc Cancer Research"],["dc.relation.issn","1538-7445"],["dc.relation.issn","0008-5472"],["dc.title","Krüppel-like Transcription Factor KLF10 Suppresses TGFβ-Induced Epithelial-to-Mesenchymal Transition via a Negative Feedback Mechanism"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]