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","1300"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Genes & Development"],["dc.bibliographiccitation.lastpage","1312"],["dc.bibliographiccitation.volume","30"],["dc.contributor.author","Nemajerova, Alice"],["dc.contributor.author","Kramer, Daniela"],["dc.contributor.author","Siller, Saul S."],["dc.contributor.author","Herr, Christian"],["dc.contributor.author","Shomroni, Orr"],["dc.contributor.author","Pena, Tonatiuh"],["dc.contributor.author","Suazo, Cristina Gallinas"],["dc.contributor.author","Glaser, Katharina"],["dc.contributor.author","Wildung, Merit"],["dc.contributor.author","Steffen, Henrik"],["dc.contributor.author","Sriraman, Anusha"],["dc.contributor.author","Oberle, Fabian"],["dc.contributor.author","Wienken, Magdalena"],["dc.contributor.author","Hennion, Magali"],["dc.contributor.author","Vidal, Ramon"],["dc.contributor.author","Royen, Bettina"],["dc.contributor.author","Alevra, Mihai"],["dc.contributor.author","Schild, Detlev"],["dc.contributor.author","Bals, Robert"],["dc.contributor.author","Doenitz, Juergen"],["dc.contributor.author","Riedel, Dietmar"],["dc.contributor.author","Bonn, Stefan"],["dc.contributor.author","Takemaru, Ken-Ichi"],["dc.contributor.author","Moll, Ute M."],["dc.contributor.author","Lize, Muriel"],["dc.date.accessioned","2018-11-07T10:13:24Z"],["dc.date.available","2018-11-07T10:13:24Z"],["dc.date.issued","2016"],["dc.description.abstract","Motile multiciliated cells (MCCs) have critical roles in respiratory health and disease and are essential for cleaning inhaled pollutants and pathogens from airways. Despite their significance for human disease, the transcriptional control that governs multiciliogenesis remains poorly understood. Here we identify TP73, a p53 homolog, as governing the program for airway multiciliogenesis. Mice with TP73 deficiency suffer from chronic respiratory tract infections due to profound defects in ciliogenesis and complete loss of mucociliary clearance. Organotypic airway cultures pinpoint TAp73 as necessary and sufficient for basal body docking, axonemal extension, and motility during the differentiation of MCC progenitors. Mechanistically, cross-species genomic analyses and complete ciliary rescue of knockout MCCs identify TAp73 as the conserved central transcriptional integrator of multiciliogenesis. TAp73 directly activates the key regulators FoxJ1, Rfx2, Rfx3, and miR34bc plus nearly 50 structural and functional ciliary genes, some of which are associated with human ciliopathies. Our results position TAp73 as a novel central regulator of MCC differentiation."],["dc.identifier.doi","10.1101/gad.279836.116"],["dc.identifier.isi","000378084000006"],["dc.identifier.pmid","27257214"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40428"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Cold Spring Harbor Lab Press, Publications Dept"],["dc.relation.issn","1549-5477"],["dc.relation.issn","0890-9369"],["dc.title","TAp73 is a central transcriptional regulator of airway multiciliogenesis"],["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","2231"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Human Molecular Genetics"],["dc.bibliographiccitation.lastpage","2246"],["dc.bibliographiccitation.volume","26"],["dc.contributor.author","Paiva, Isabel"],["dc.contributor.author","Pinho, Raquel"],["dc.contributor.author","Pavlou, Maria Angeliki"],["dc.contributor.author","Hennion, Magali"],["dc.contributor.author","Wales, Pauline"],["dc.contributor.author","Schütz, Anna-Lena"],["dc.contributor.author","Rajput, Ashish"],["dc.contributor.author","Szegő, Éva M."],["dc.contributor.author","Kerimoglu, Cemil"],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Rego, Ana Cristina"],["dc.contributor.author","Fischer, André"],["dc.contributor.author","Bonn, Stefan"],["dc.contributor.author","Outeiro, Tiago F."],["dc.date.accessioned","2018-04-23T11:47:17Z"],["dc.date.available","2018-04-23T11:47:17Z"],["dc.date.issued","2017"],["dc.description.abstract","Alpha-synuclein (aSyn) is considered a major culprit in Parkinson’s disease (PD) pathophysiology. However, the precise molecular function of the protein remains elusive. Recent evidence suggests that aSyn may play a role on transcription regulation, possibly by modulating the acetylation status of histones. Our study aimed at evaluating the impact of wild-type (WT) and mutant A30P aSyn on gene expression, in a dopaminergic neuronal cell model, and decipher potential mechanisms underlying aSyn-mediated transcriptional deregulation. We performed gene expression analysis using RNA-sequencing in Lund Human Mesencephalic (LUHMES) cells expressing endogenous (control) or increased levels of WT or A30P aSyn. Compared to control cells, cells expressing both aSyn variants exhibited robust changes in the expression of several genes, including downregulation of major genes involved in DNA repair. WT aSyn, unlike A30P aSyn, promoted DNA damage and increased levels of phosphorylated p53. In dopaminergic neuronal cells, increased aSyn expression led to reduced levels of acetylated histone 3. Importantly, treatment with sodium butyrate, a histone deacetylase inhibitor (HDACi), rescued WT aSyn-induced DNA damage, possibly via upregulation of genes involved in DNA repair. Overall, our findings provide novel and compelling insight into the mechanisms associated with aSyn neurotoxicity in dopaminergic cells, which could be ameliorated with an HDACi. Future studies will be crucial to further validate these findings and to define novel possible targets for intervention in PD."],["dc.identifier.doi","10.1093/hmg/ddx114"],["dc.identifier.gro","3142201"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13321"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.status","final"],["dc.relation.issn","0964-6906"],["dc.title","Sodium butyrate rescues dopaminergic cells from alpha-synuclein-induced transcriptional deregulation and DNA damage"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["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"]]

[["dc.bibliographiccitation.firstpage","102"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Neuroscience"],["dc.bibliographiccitation.lastpage","110"],["dc.bibliographiccitation.volume","19"],["dc.contributor.author","Halder, Rashi"],["dc.contributor.author","Hennion, Magali"],["dc.contributor.author","Vidal, Ramon O."],["dc.contributor.author","Shomroni, Orr"],["dc.contributor.author","Rahman, Raza-Ur"],["dc.contributor.author","Rajput, Ashish"],["dc.contributor.author","Centeno, Tonatiuh Pena"],["dc.contributor.author","van Bebber, Frauke"],["dc.contributor.author","Capece, Vincenzo"],["dc.contributor.author","Garcia Vizcaino, Julio C."],["dc.contributor.author","Schuetz, Anna-Lena"],["dc.contributor.author","Burkhardt, Susanne"],["dc.contributor.author","Benito, Eva"],["dc.contributor.author","Navarro Sala, Magdalena"],["dc.contributor.author","Bahari Javan, Sanaz"],["dc.contributor.author","Haass, Christian"],["dc.contributor.author","Schmid, Bettina"],["dc.contributor.author","Fischer, André"],["dc.contributor.author","Bonn, Stefan"],["dc.date.accessioned","2018-05-30T15:01:05Z"],["dc.date.available","2018-05-30T15:01:05Z"],["dc.date.issued","2016"],["dc.description.abstract","The ability to form memories is a prerequisite for an organism's behavioral adaptation to environmental changes. At the molecular level, the acquisition and maintenance of memory requires changes in chromatin modifications. In an effort to unravel the epigenetic network underlying both short- and long-term memory, we examined chromatin modification changes in two distinct mouse brain regions, two cell types and three time points before and after contextual learning. We found that histone modifications predominantly changed during memory acquisition and correlated surprisingly little with changes in gene expression. Although long-lasting changes were almost exclusive to neurons, learning-related histone modification and DNA methylation changes also occurred in non-neuronal cell types, suggesting a functional role for non-neuronal cells in epigenetic learning. Finally, our data provide evidence for a molecular framework of memory acquisition and maintenance, wherein DNA methylation could alter the expression and splicing of genes involved in functional plasticity and synaptic wiring."],["dc.identifier.doi","10.1038/nn.4194"],["dc.identifier.pmid","26656643"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/14808"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1546-1726"],["dc.title","DNA methylation changes in plasticity genes accompany the formation and maintenance of memory"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]