Group Seiser

Chromatin modifiers in development and disease

The SEISER Lab moved to the Center for Anatomy and Cell Biology at the Medical University of Vienna.

Email: christian.seiser [AT] meduniwien.ac [DOT] at

Web: http://anatomieundzellbiologie.meduniwien.ac.at/cell-biology/epigenetics-and-rna-biology/group-seiser/?L=1 

 

New address: 
Medical University of Vienna, Center for Anatomy & Cell Biology
Department of Cell and Developmental Biology, Unit of Epigenetics & RNA Biology
Schwarzspanierstrasse 17-I, 1090 Vienna, Austria

DNA, the carrier of genetic information in our cells, is organized with the help of histone proteins as chromatin. Histone modifications affect the chromatin structure and thereby  important biological processes such as transcription, replication and DNA repair. Our group is specifically interested in the role of histone deacetylases (HDACs) in development and disease. HDAC inhibitor treatment of tumor cells leads to cell cycle arrest, differentiation or apoptosis. Therefore, HDACs are potential targets for anti-tumor drugs and several HDAC inhibitors are currently tested in clinical trials. HDACs are considered as transcriptional co-repressors and 18 members of the HDAC family have been identified in mammalian cells.

We have originally identified mouse HDAC1 as growth factor inducible gene in cytolytic T cells (Bartl et al., 1997). HDAC1 gene disruption in mice leads to reduced proliferation and severe developmental problems resulting in embryonic lethality of HDAC1 knockout mice (Lagger et al., 2002). One crucial function of HDAC1 in the context of proliferation control is the repression of the CDK inhibitor p21/WAF1 suggesting a potential role of HDAC1 in tumorigenesis (Zupkovitz et al., 2010). Surprisingly, absence or reduced expression of HDAC1 in murine or human teratomas led to increased proliferation and reduced differentiation and was linked with a more malignant phenotype (Lagger et al., 2010). We are currently studying the function of HDAC enzymes in different cell types and tissues by using conditional HDAC knockout mice.

In a second project, we examine the role of histone phosphorylation during the activation of mammalian genes by stress and growth factors. The presence of histone H3 phosphorylation marks at the regulatory regions of several mammalian genes correlates with the induced expression of a dozens of target genes in mammalian cells. We have recently shown that 14-3-3 zeta can act as reader protein for S10- and S28-phosphorylated histone H3 (Winter et al., 2008a; Winter et al., 2008b). We have now identified the phosphatase PP2A as chromatin associated transcriptional repressor, which removes the active chromatin mark from specific target genes (Simboeck et al., 2010). In the near future, we plan to analyze the genome wide presence of H3 phosphorylation marks in mouse cells.

Bartl, S., Taplick , J., Lagger, G., Khier, H., Kuchler, K. and Seiser, C. (1997) Identification of mouse histone deacetylase 1 as a growth factor-inducible gene. Mol. Cell. Biol., 17, 5033-5043.

Lagger, G., O'Carroll, D., Rembold, M., Khier, H., Tischler, J., Weitzer, G., Schuettengruber, B., Hauser, C., Brunmeir, R., Jenuwein, T. and Seiser, C. (2002) Essential function of histone deacetylase 1 in proliferation control and CDK inhibitor repression. Embo J, 21, 2672-2681.

Lagger, S., Meunier, D., Mikula, M., Brunmeir, R., Schlederer, M., Artaker, M., Pusch, O., Egger, G., Hagelkruys, A., Mikulits, W., Weitzer, G., Muellner, E.W., Susani, M., Kenner, L. and Seiser, C. (2010) Crucial function of histone deacetylase 1 for differentiation of teratomas in mice and humans.EMBO J, 29, 3992-4007.

Simboeck, E., Sawicka, A., Zupkovitz, G., Senese, S., Winter, S., Dequiedt, F., Ogris, E., Di Croce, L., Chiocca, S. and Seiser, C. (2010) A phosphorylation switch regulates the transcriptional activation of cell cycle regulator p21 by histone deacetylase inhibitors. J Biol Chem, 285, 41062-41073.

Winter, S., Fischle, W. and Seiser, C. (2008a) Modulation of 14-3-3 interaction with phosphorylated histone H3 by combinatorial modification patterns. Cell Cycle, 7, 1336-1342.

Winter, S., Simboeck, E., Fischle, W., Zupkovitz, G., Dohnal, I., Mechtler, K., Ammerer, G. and Seiser, C. (2008b) 14-3-3 Proteins recognize a histone code at histone H3 and are required for transcriptional activation. Embo J, 27, 88-99.

Zupkovitz, G., Grausenburger, R., Brunmeir, R., Senese, S., Tischler, J., Jurkin, J., Rembold, M., Meunier, D., Egger, G., Lagger, S., Chiocca, S., Propst, F., Weitzer, G. and Seiser, C. (2010) The cyclin-dependent kinase inhibitor p21 is a crucial target for histone deacetylase 1 as a regulator of cellular proliferation. Mol Cell Biol, 30, 1171-1181.

 

Publications since 2006

Segré, Chiara V; Senese, Silvia; Loponte, Sara; Santaguida, Stefano; Soffientini, Paolo; Grigorean, Gabriela; Cinquanta, Mario; Ossolengo, Giuseppe; Seiser, Christian; Chiocca, Susanna (2016). A monoclonal antibody specific for prophase phosphorylation of histone deacetylase 1: a readout for early mitotic cells. mAbs.;8(1):37-42. PMID: 26467746

Loponte, Sara; Segré, Chiara V; Senese, Silvia; Miccolo, Claudia; Santaguida, Stefano; Deflorian, Gianluca; Citro, Simona; Mattoscio, Domenico; Pisati, Federica; Moser, Mirjam A; Visintin, Rosella; Seiser, Christian; Chiocca, Susanna (2016). Dynamic phosphorylation of Histone Deacetylase 1 by Aurora kinases during mitosis regulates zebrafish embryos development. Scientific reports.;6:30213. PMID: 27458029

Sakaguchi, Shinya; Hombauer, Matthias; Hassan, Hammad; Tanaka, Hirokazu; Yasmin, Nighat; Naoe, Yoshinori; Bilic, Ivan; Moser, Mirjam A; Hainberger, Daniela; Mayer, Herbert; Seiser, Christian; Bergthaler, Andreas; Taniuchi, Ichiro; Ellmeier, Wilfried (2015). A novel Cd8-cis-regulatory element preferentially directs expression in CD44hiCD62L+ CD8+ T cells and in CD8αα+ dendritic cells. J Leukoc Biol;97(4):635-44. PMID: 25548254

Hagelkruys, Astrid; Mattes, Katharina; Moos, Verena; Rennmayr, Magdalena; Ringbauer, Manuela; Sawicka, Anna; Seiser, Christian (2015). Essential Nonredundant Function of the Catalytic Activity of Histone Deacetylase 2 in Mouse Development. MOL CELL BIOL;36(3):462-74. PMID:26598605

Moser, Mirjam Andrea; Hagelkruys, Astrid; Seiser, Christian (2014). Transcription and beyond: the role of mammalian class I lysine deacetylases. CHROMOSOMA;123(1-2):67-78. PMID:24170248

Hagelkruys, Astrid; Lagger, Sabine; Krahmer, Julia; Leopoldi, Alexandra; Artaker, Matthias; Pusch, Oliver; Zezula, Jürgen; Weissmann, Simon; Xie, Yunli; Schöfer, Christian; Schlederer, Michaela; Brosch, Gerald; Matthias, Patrick; Selfridge, Jim; Lassmann, Hans; Knoblich, Jürgen A; Seiser, Christian (2014). A single allele of Hdac2 but not Hdac1 is sufficient for normal mouse brain development in the absence of its paralog. DEVELOPMENT;141(3):604-16. PMID: 24449838

Boucheron, Nicole; Tschismarov, Roland; Goeschl, Lisa; Moser, Mirjam A; Lagger, Sabine; Sakaguchi, Shinya; Winter, Mircea; Lenz, Florian; Vitko, Dijana; Breitwieser, Florian P; Müller, Lena; Hassan, Hammad; Bennett, Keiryn L; Colinge, Jacques; Schreiner, Wolfgang; Egawa, Takeshi; Taniuchi, Ichiro; Matthias, Patrick; Seiser, Christian; Ellmeier, Wilfried (2014). CD4(+) T cell lineage integrity is controlled by the histone deacetylases HDAC1 and HDAC2. NAT IMMUNOL;15(5):439-48. PMID: 24681565

Sawicka, Anna; Seiser, Christian (2014). Sensing core histone phosphorylation - A matter of perfect timing. BBA-GENE REGUL MECH;1839(8):711-718. PMID: 24747175

Sawicka, Anna; Hartl, Dominik; Goiser, Malgorzata; Pusch, Oliver; Stocsits, Roman R; Tamir, Ido; Mechtler, Karl; Seiser, Christian (2014). H3S28 phosphorylation is a hallmark of the transcriptional response to cellular stress. GENOME RES;24(11):1808-20. PMID: 25135956

Tschismarov, Roland; Firner, Sonja; Gil-Cruz, Cristina; Göschl, Lisa; Boucheron, Nicole; Steiner, Günter; Matthias, Patrick; Seiser, Christian; Ludewig, Burkhard; Ellmeier, Wilfried (2014). HDAC1 Controls CD8+ T Cell Homeostasis and Antiviral Response. PLOS ONE;9(10):e110576. PMID:25333902

Hoebaus, Julia; Heher, Philipp; Gottschamel, Teresa; Scheinast, Matthias; Auner, Harmen; Walder, Diana; Wiedner, Marc; Taubenschmid, Jasmin; Miksch, Maximilian; Sauer, Thomas; Schultheis, Martina; Kuzmenkin, Alexey; Seiser, Christian; Hescheler, Juergen; Weitzer, Georg (2013).Embryonic Stem Cells Facilitate the Isolation of Persistent Clonal Cardiovascular Progenitor Cell Lines and Leukemia Inhibitor Factor Maintains Their Self-Renewal and Myocardial Differentiation Potential in vitro. Cells Tissues Organs;197(4):249-68. PMID: 23343517

Murko, Christina; Lagger, Sabine; Steiner, Marianne; Seiser, Christian; Schoefer, Christian; Pusch, Oliver (2013). Histone deacetylase inhibitor Trichostatin A induces neural tube defects and promotes neural crest specification in the chicken neural tube. DIFFERENTIATION;85(1-2):55-66. PMID: 23328540

He, Shihua; Khan, Dilshad H; Winter, Stefan; Seiser, Christian; Davie, James R (2013). Dynamic distribution of HDAC1 and HDAC2 during mitosis: Association with F-actin. J CELL PHYSIOL;228(7):1525-35. PMID: 23280436

Khan, Dilshad H; He, Shihua; Yu, Jenny; Winter, Stefan; Cao, Wenguang; Seiser, Christian; Davie, James R (2013). Protein kinase CK2 regulates the dimerization of histone deacetylase 1 (HDAC1) and HDAC2 during mitosis. J BIOL CHEM;288(23):16518-28. PMID: 23612983

Winter, Mircea; Moser, Mirjam A; Meunier, Dominique; Fischer, Carina; Machat, Georg; Mattes, Katharina; Lichtenberger, Beate M; Brunmeir, Reinhard; Weissmann, Simon; Murko, Christina; Humer, Christina; Meischel, Tina; Brosch, Gerald; Matthias, Patrick; Sibilia, Maria; Seiser, Christian (2013). Divergent roles of HDAC1 and HDAC2 in the regulation of epidermal development and tumorigenesis. EMBO J;32(24):3176-91. PMID: 24240174

Citro, Simona; Jaffray, Ellis; Hay, Ronald T; Seiser, Christian; Chiocca, Susanna (2013). A role for paralog-specific sumoylation in histone deacetylase 1 stability. J MOL CELL BIOL;5(6):416-27. PMID: 24068740

Koerner MV, Pauler FM, Hudson QJ, Santoro F, Sawicka A, Guenzl PM, Stricker SH, Schichl YM, Latos PA, Klement RM, Warczok KE, Wojciechowski J, Seiser C, Kralovics R, Barlow DP. (2012). A Downstream CpG Island Controls Transcript Initiation and Elongation and the Methylation State of the Imprinted Airn Macro ncRNA Promoter PLOS GENET;8(3):e1002540. PMID:22396659

Fonseca, João Pedro; Steffen, Philipp A; Müller, Stefan; Lu, James; Sawicka, Anna; Seiser, Christian; Ringrose, Leonie (2012). In vivo Polycomb kinetics and mitotic chromatin binding distinguish stem cells from differentiated cells. GENE DEV;26(8):857-71. PMID: 22508729

Sawicka, Anna; Seiser, Christian (2012). Histone H3 phosphorylation - A versatile chromatin modification for different occasions. BIOCHIMIE. PMID: 22564826

Koerner, Martha V; Pauler, Florian M; Hudson, Quanah J; Santoro, Federica; Sawicka, Anna; Guenzl, Philipp M; Stricker, Stefan H; Schichl, Yvonne M; Latos, Paulina A; Klement, Ruth M; Warczok, Katarzyna E; Wojciechowski, Jacek; Seiser, Christian; Kralovics, Robert; Barlow, Denise P (2012). A downstream CpG island controls transcript initiation and elongation and the methylation state of the imprinted Airn macro ncRNA promoter. PLOS GENET;8(3):e1002540. PMID: 22396659

 Laimer, Daniela; Dolznig, Helmut; Kollmann, Karoline; Vesely, Paul W; Schlederer, Michaela; Merkel, Olaf; Schiefer, Ana-Iris; Hassler, Melanie R; Heider, Susi; Amenitsch, Lena; Thallinger, Christiane; Staber, Philipp B; Simonitsch-Klupp, Ingrid; Artaker, Matthias; Lagger, Sabine; Turner, Suzanne D; Pileri, Stefano; Piccaluga, Pier Paolo; Valent, Peter; Messana, Katia; Landra, Indira; Weichhart, Thomas; Knapp, Sylvia; Shehata, Medhat; Todaro, Maria; Sexl, Veronika; Höfler, Gerald; Piva, Roberto; Medico, Enzo; Ruggeri, Bruce A; Cheng, Mangeng; Eferl, Robert; Egger, Gerda; Penninger, Josef M; Jaeger, Ulrich; Moriggl, Richard; Inghirami, Giorgio; Kenner, Lukas (2012).PDGFR blockade is a rational and effective therapy for NPM-ALK-driven lymphomas. Nature medicine.;18(11):1699-704. PMID: 23064464

Jurkin, Jennifer; Zupkovitz, Gordin; Lagger, Sabine; Grausenburger, Reinhard; Hagelkruys, Astrid; Kenner, Lukas; Seiser, Christian (2011). Distinct and redundant functions of histone deacetylases HDAC1 and HDAC2 in proliferation and tumorigenesis. CELL CYCLE;10(3):406-12. PMID: 21270520

Hagelkruys, Astrid; Sawicka, Anna; Rennmayr, Magdalena; Seiser, Christian (2011). The biology of HDAC in cancer: the nuclear and epigenetic components. Handb Exp Pharmacol;206:13-37. PMID: 21879444

Zupkovitz, Gordin; Grausenburger, Reinhard; Brunmeir, Reinhard; Senese, Silvia; Tischler, Julia; Jurkin, Jennifer; Rembold, Martina; Meunier, Dominique; Egger, Gerda; Lagger, Sabine; Chiocca, Susanna; Propst, Fritz; Weitzer, Georg; Seiser, Christian (2010). The cyclin-dependent kinase inhibitor p21 is a crucial target for histone deacetylase 1 as a regulator of cellular proliferation. MOL CELL BIOL. PMID: 20028735

Brunmeir, Reinhard; Lagger, Sabine; Simboeck, Elisabeth; Sawicka, Anna; Egger, Gerda; Hagelkruys, Astrid; Zhang, Yu; Matthias, Patrick; Miller, Wolfgang J; Seiser, Christian (2010).Epigenetic regulation of a murine retrotransposon by a dual histone modification mark. PLOS GENET. PMID: 20442873

Grausenburger, Reinhard; Bilic, Ivan; Boucheron, Nicole; Zupkovitz, Gordin; El-Housseiny, Lamia; Tschismarov, Roland; Zhang, Yu; Rembold, Martina; Gaisberger, Martin; Hartl, Arnulf; Epstein, Michelle M; Matthias, Patrick; Seiser, Christian; Ellmeier, Wilfried (2010). Conditional deletion of histone deacetylase 1 in T cells leads to enhanced airway inflammation and increased Th2 cytokine production. J IMMUNOL. PMID: 20702731

Yamaguchi, Teppei; Cubizolles, Fabien; Zhang, Yu; Reichert, Nina; Kohler, Hubertus; Seiser, Christian; Matthias, Patrick (2010). Histone deacetylases 1 and 2 act in concert to promote the G1-to-S progression. GENE DEV. PMID: 20194438

Simboeck, Elisabeth; Sawicka, Anna; Zupkovitz, Gordin; Senese, Silvia; Winter, Stefan; Dequiedt, Franck; Ogris, Egon; Di Croce, Luciano; Chiocca, Susanna; Seiser, Christian (2010). A phosphorylation switch regulates the transcriptional activation of cell cycle regulator p21 by histone deacetylase inhibitors. J BIOL CHEM. PMID: 20952396

Lagger, Sabine; Meunier, Dominique; Mikula, Mario; Brunmeir, Reinhard; Schlederer, Michaela; Artaker, Matthias; Pusch, Oliver; Egger, Gerda; Hagelkruys, Astrid; Mikulits, Wolfgang; Weitzer, Georg; Muellner, Ernst W; Susani, Martin; Kenner, Lukas; Seiser, Christian (2010). Crucial function of histone deacetylase 1 for differentiation of teratomas in mice and humans. EMBO J. PMID:20967026

Jawerka, Melanie; Colak, Dilek; Dimou, Leda; Spiller, Carmen; Lagger, Sabine; Montgomery, Rusty L; Olson, Eric N; Wurst, Wolfgang; Göttlicher, Martin; Götz, Magdalena (2010). The specific role of histone deacetylase 2 in adult neurogenesis. NEURON GLIA BIOL. PMID: 20388229

Murko, Christina; Lagger, Sabine; Steiner, Marianne; Seiser, Christian; Schoefer, Christian; Pusch, Oliver (2010). Expression of class I histone deacetylases during chick and mouse development. INT J DEV BIOL. PMID: 20979029

Blüml, Stephan; Zupkovitz, Gordin; Kirchberger, Stefanie; Seyerl, Maria; Bochkov, Valery N; Stuhlmeier, Karl; Majdic, Otto; Zlabinger, Gerhard J; Seiser, Christian; Stöckl, Johannes (2009).Epigenetic regulation of dendritic cell differentiation and function by oxidized phospholipids.BLOOD. PMID: 19864645

Brunmeir, Reinhard; Lagger, Sabine; Seiser, Christian (2009). Histone deacetylase HDAC1/HDAC2-controlled embryonic development and cell differentiation. INT J DEV BIOL. PMID: 19412887

Winter, Stefan; Simboeck, Elisabeth; Fischle, Wolfgang; Zupkovitz, Gordin; Dohnal, Ilse; Mechtler, Karl; Ammerer, Gustav; Seiser, Christian (2008). 14-3-3 proteins recognize a histone code at histone H3 and are required for transcriptional activation. EMBO J. PMID: 18059471

Winter, Stefan; Fischle, Wolfgang; Seiser, Christian (2008). Modulation of 14-3-3 interaction with phosphorylated histone H3 by combinatorial modification patterns. CELL CYCLE. PMID:18418070

Senese, Silvia; Zaragoza, Katrin; Minardi, Simone; Muradore, Ivan; Ronzoni, Simona; Passafaro, Alfonso; Bernard, Loris; Draetta, Giulio F; Alcalay, Myriam; Seiser, Christian; Chiocca, Susanna (2007). Role for histone deacetylase 1 in human tumor cell proliferation. MOL CELL BIOL. PMID: 17470557

Ramsauer, Katrin; Farlik, Matthias; Zupkovitz, Gordin; Seiser, Christian; Kröger, Andrea; Hauser, Hansjörg; Decker, Thomas (2007). Distinct modes of action applied by transcription factors STAT1 and IRF1 to initiate transcription of the IFN-gamma-inducible gbp2 gene. P NATL ACAD SCI USA. PMID: 17293456

Zupkovitz, Gordin; Tischler, Julia; Posch, Markus; Sadzak, Iwona; Ramsauer, Katrin; Egger, Gerda; Grausenburger, Reinhard; Schweifer, Norbert; Chiocca, Susanna; Decker, Thomas; Seiser, Christian (2006). Negative and positive regulation of gene expression by mouse histone deacetylase 1.MOL CELL BIOL. PMID: 16940178