Hennion, Magali

[["dc.bibliographiccitation.firstpage","5739"],["dc.bibliographiccitation.issue","17"],["dc.bibliographiccitation.journal","Cancer Research"],["dc.bibliographiccitation.lastpage","5753"],["dc.bibliographiccitation.volume","71"],["dc.contributor.author","Prenzel, Tanja"],["dc.contributor.author","Begus-Nahrmann, Yvonne"],["dc.contributor.author","Kramer, Frank"],["dc.contributor.author","Hennion, Magali"],["dc.contributor.author","Hsu, Chieh"],["dc.contributor.author","Gorsler, Theresa"],["dc.contributor.author","Hintermair, Corinna"],["dc.contributor.author","Eick, Dirk"],["dc.contributor.author","Kremmer, Elisabeth"],["dc.contributor.author","Simons, Mikael"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Johnsen, Steven Arthur"],["dc.date.accessioned","2018-11-07T08:52:42Z"],["dc.date.available","2018-11-07T08:52:42Z"],["dc.date.issued","2011"],["dc.description.abstract","The estrogen receptor-alpha (ER alpha) determines the phenotype of breast cancers where it serves as a positive prognostic indicator. ER alpha is a well-established target for breast cancer therapy, but strategies to target its function remain of interest to address therapeutic resistance and further improve treatment. Recent findings indicate that proteasome inhibition can regulate estrogen-induced transcription, but how ER alpha function might be regulated was uncertain. In this study, we investigated the transcriptome-wide effects of the proteasome inhibitor bortezomib on estrogen-regulated transcription in MCF7 human breast cancer cells and showed that bortezomib caused a specific global decrease in estrogen-induced gene expression. This effect was specific because gene expression induced by the glucocorticoid receptor was unaffected by bortezomib. Surprisingly, we observed no changes in ERa recruitment or assembly of its transcriptional activation complex on ERa target genes. Instead, we found that proteasome inhibition caused a global decrease in histone H2B monoubiquitination (H2Bub1), leading to transcriptional elongation defects on estrogen target genes and to decreased chromatin dynamics overall. In confirming the functional significance of this link, we showed that RNA interference-mediated knockdown of the H2B ubiquitin ligase RNF40 decreased ER alpha-induced gene transcription. Surprisingly, RNF40 knockdown also supported estrogen-independent cell proliferation and activation of cell survival signaling pathways. Most importantly, we found that H2Bub1 levels decrease during tumor progression. H2Bub1 was abundant in normal mammary epithelium and benign breast tumors but absent in most malignant and metastatic breast cancers. Taken together, our findings show how ERa activity is blunted by bortezomib treatment as a result of reducing the downstream ubiquitin-dependent function of H2Bub1. In supporting a tumor suppressor role for H2Bub1 in breast cancer, our findings offer a rational basis to pursue H2Bub1-based therapies for future management of breast cancer. Cancer Res; 71(17); 5739-53. (C)2011 AACR."],["dc.identifier.doi","10.1158/0008-5472.CAN-11-1896"],["dc.identifier.isi","000294454700017"],["dc.identifier.pmid","21862633"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/22232"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Cancer Research"],["dc.relation.issn","0008-5472"],["dc.title","Estrogen-Dependent Gene Transcription in Human Breast Cancer Cells Relies upon Proteasome-Dependent Monoubiquitination of Histone H2B"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["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","705"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Molecular Cell"],["dc.bibliographiccitation.lastpage","713"],["dc.bibliographiccitation.volume","46"],["dc.contributor.author","Karpiuk, Oleksandra"],["dc.contributor.author","Najafova, Zeynab"],["dc.contributor.author","Kramer, Frank"],["dc.contributor.author","Hennion, Magali"],["dc.contributor.author","Galonska, Christina"],["dc.contributor.author","Koenig, Annekatrin"],["dc.contributor.author","Snaidero, Nicolas"],["dc.contributor.author","Vogel, Tanja"],["dc.contributor.author","Shchebet, Andrei"],["dc.contributor.author","Begus-Nahrmann, Yvonne"],["dc.contributor.author","Kassem, Moustapha"],["dc.contributor.author","Simons, Mikael"],["dc.contributor.author","Shcherbata, Halyna R."],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Johnsen, Steven Arthur"],["dc.date.accessioned","2018-11-07T09:09:17Z"],["dc.date.available","2018-11-07T09:09:17Z"],["dc.date.issued","2012"],["dc.description.abstract","Extensive changes in posttranslational histone modifications accompany the rewiring of the transcriptional program during stem cell differentiation. However, the mechanisms controlling the changes in specific chromatin modifications and their function during differentiation remain only poorly understood. We show that histone H2B monoubiquitination (H2Bubl) significantly increases during differentiation of human mesenchymal stem cells (hMSCs) and various lineage-committed precursor cells and in diverse organisms. Furthermore, the H2B ubiquitin ligase RNF40 is required for the induction of differentiation markers and transcriptional reprogramming of hMSCs. This function is dependent upon CDK9 and the WAC adaptor protein, which are required for H2B monoubiquitination. Finally, we show that RNF40 is required for the resolution of the H3K4me3/H3K27me3 bivalent poised state on lineage-specific genes during the transition from an inactive to an active chromatin conformation. Thus, these data indicate that H2Bubl is required for maintaining multipotency of hMSCs and plays a central role in controlling stem cell differentiation."],["dc.identifier.doi","10.1016/j.molcel.2012.05.022"],["dc.identifier.isi","000305095400018"],["dc.identifier.pmid","22681891"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/26221"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Cell Press"],["dc.relation.issn","1097-2765"],["dc.title","The Histone H2B Monoubiquitination Regulatory Pathway Is Required for Differentiation of Multipotent Stem Cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]