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Christian J. Janzen Profile Page
Research
| Research Topic: | Histone Methylation of Trypanosomes During Differentiation and Cell Cycle Control |
| Affiliation: | LMU |
| Research Area: | Cell Biology |
| Faculty Status: | IMPRS Junior Group |
| Research Methods: | Biochemistry;Cell Biology;Genetics;Molecular Biology |
| Homepage: | www.genetik.biologie.uni-muenchen.de/research/janzen/index.html |
| Research Summary: | Trypanosomes are mammalian pathogens with a complex parasitic life cycle in different hosts. Many cellular functions, including cell cycle control and developmental differentiation, have to be carefully coordinated and adapted in order to survive in these different environments. Although many conserved cell cycle regulators are also present in trypanosomes, substantial divergence of their functions and other regulatory mechanisms seem to have evolved in trypanosomes. One novel mechanism of cell cycle regulation appears to involve changes in chromatin structure mediated through dynamic methylation of histone H3K76 by two members of the DOT1 methyltransferase family (DOT1A and DOT1B). Di-methylation of H3K76 (H3K76me2) by DOT1A is only detectable during mitosis and cytokinesis and RNAi-mediated depletion of DOT1A causes severe cell cycle defects. Similarly, over-expression of DOT1B, which is responsible for tri-methylation of H3K76, forces the parasites into premature cytokinesis without completion of karyokinesis. In one of our projects, we want to test our hypothesis that coordinated regulation of DOT1A and DOT1B activity controls cell cycle progression in trypanosomes. Furthermore, we have evidence that DOT1B is involved in developmental differentiation. In our second project, we want to investigate if changes in chromatin structure regulate gene expression during the differentiation process in T. brucei. |
| Selected Publications: | Figueiredo, L.M., Cross, G.A.M., and Janzen, C.J. (2009). Epigenetic regulation in African trypanosomes: a new kid on the block. Nature Reviews Microbiology 7, 504-513. Figueiredo, L.M., Janzen, C.J., and Cross, G.A.M. (2008). A histone methyltransferase modulates antigenic variation in African trypanosomes. Plos Biology 6, 1539-1548. Siegel, T.N., Kawahara, T., DeGrasse, J.A., Janzen, C.J., Horn, D., and Cross, G.A.M. (2008). Acetylation of histone H4K4 is cell cycle regulated and mediated by HAD in Trypanosoma brucei. Molecular Microbiology 67, 762-771. Mandava, V., Janzen, C.J., and Cross, G.A.M. (2008). Trypanosome H2Bv replaces H2B in nucleosomes enriched for H3K4 and K76 trimethylation. Biochemical and Biophysical Research Communications 368, 846-851. Mandava, V., Fernandez, J.P., Deng, H., Janzen, C.J., Hake, S.B., and Cross, G.A.M. (2007). Histone modifications in Trypanosoma brucei. Molecular and Biochemical Parasitology 156, 41-50. Janzen, C.J., van Deursen, F., Shi, H.F., Cross, G.A.M., Matthews, K.R., and Ullu, E. (2006). Expression site silencing and life-cycle progression appear normal in Argonaute1-deficient Trypanosoma brucei. Molecular and Biochemical Parasitology 149, 102-107. Janzen, C.J., Hake, S.B., Lowell, J.E., and Cross, G.A.M. (2006). Selective di- or trimethylation of histone H3 lysine 76 by two DOT1 homologs is important for cell cycle regulation in Trypanosoma brucei. Molecular Cell 23, 497-507. Janzen, C.J., Fernandez, J.P., Deng, H.T., Diaz, R., Hake, S.B., and Cross, G.A.M. (2006). Unusual histone modifications in Trypanosoma brucei. Febs Letters 580, 2306-2310. Lowell, J.E., Kaiser, F., Janzen, C.J., and Cross, G.A.M. (2005). Histone H2AZ dimerizes with a novel variant H2B and is enriched at repetitive DNA in Trypanosoma brucei. Journal of Cell Science 118, 5721-5730. Janzen, C.J., Lander, F., Dreesen, O., and Cross, G.A.M. (2004). Telomere length regulation and transcriptional silencing in KU80-deficient Trypanosoma brucei. Nucleic Acids Research 32, 6575-6584. |
Curriculum Vitae
| Curriculum Vitae: | RWTH, Aachen, Study of Biology, 1990-1996 University of Freiburg, Institute of Microbiology and Hygiene, PhD, 1996-2000 Rockefeller University, New York, USA, Laboratory of Molecular Parasitology, Post-doctoral fellow, 2000-2005 Rockefeller University, New York, USA, Research associate, 2005-2006 University of Munich (LMU), Department Biology I, Genetics, Munich, Independent group leader, since 2006 |
Contact
| Contact: | Christian Janzen University of Munich (LMU) Department Biology I, Genetics Großharderner Str. 2-4 82152 Martinsried Germany Phone.: +49 89 2180 74501 |
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