Nagarajan, Sankari

[["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","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"]]