Topology of genes in mammalian cell nuclei with special emphasis on the MLL gene and its translocation partners [Elektronische Ressource] / presented by Andrea Eveline Murmann

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• Publié par: ruprecht-karls-universitat_heidelberg
• Publié le: 01 janvier 2005
• Nombre de lectures: 35
• Langue: English
• Poids de l'ouvrage: 6 Mo

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Topology of genes in mammalian cell nuclei
with special emphasis on
the MLL gene
and its translocation partners
Andrea Eveline MurmannDissertation
submitted to the
Combined Faculties for the Natural Sciences and for Mathematics
of the Ruperto-Carola University of Heidelberg, Germany
for the degree of
Doctor of Natural Sciences
Presented by
Diplom Biologist: Andrea Eveline Murmann
born in: Kronach, Oberfranken, Germany
Oral examination: 21.12.2004:Topology of genes in mammalian cell nuclei
with special emphasis on
the MLL gene
and its translocation partners
Referees: Prof. Dr. Werner Buselmaier
Prof. Dr. Peter LichterThis work was carried out at the German Cancer Research Center (DKFZ) in
Heidelberg in the Division of Molecular Genetics (December 1998 to July 1999)
and at the University of Chicago in the Department of Medicine, Section
Hematology/Oncology (January 2000 to December 2004) under the scientific
guidance of Prof. Dr. Peter Lichter and Prof. Dr. Janet D. Rowley.Darwin said that Nature couldn’t make any jumps, natura non facit saltum.
To Johannes and Julie, the two most wonderful presents of my livePublications
Vogel R., R. Viereck, A. Murmann, T. Rausch. 1999. Cloning of a higher plant elongation
factor 2 cDNA: Expression of eEF2 and a subunit of eEF1B in sugar beet cells during
phosphate and carbohydrate starvation. J Plant Physiol. 154:192-196.
Algeciras-Schimnich ,A., L. Shen, B.C. Barnhart, A.E. Murmann, J.K. Burkhardt, M.E.
Peter. 2002. Molecular ordering of the initial signaling events of CD95. Mol Cell Biol
22:207-20.
Scheuermann M.O., A.E. Murmann, K. Richter, S. Görisch, H. Herrmann, P. Lichter.
Characterization of the ICD compartment in mammalian cells with distinctly different
karyotype, in preparation.
Murmann A.E., A. Mincheva, M. Scheuermann, M. Gauthier, F. Yang, A. Fischer, E.
Carpenter, J.D. Rowley, P. Lichter. Comparative mapping of bovine loci to Indian and
Chinese muntjac chromosomes by FISH, in preparation.
Murmann A.E., J. Gao, M. Encinosa, M.E. Peter, R. Eils, P. Lichter, J.D. Rowley. Gene
density within 2 Mbp of a locus determines its 3D position in the interphase nucleus of
hematopoietic cells, in preparation.
Gao J, A.E. Murmann, J.D. Rowley, P. Lichter, R. Eils. Three-dimensional quantitative tools
to analyze the spatial arrangement of translocation partner gene, in preparation.
Posters
Spatial organization of chromosomal domains in the interphase nucleus of Muntiacus
muntjak-fibroblasts. Murmann A.E., P.L. Strissel, R. Strick, S. Lampel, P. Lichter, J.D.
Rowley. Biological Science and Learning Center, 2001, University of Chicago, Chicago, IL.
The structure of the interchromosomal domain (ICD) compartment is similar in mammalian
nuclei from species with very different chromosomal organization. Scheuermann M.O., A.E.
Murmann, K. Richter, H. Herrmann, P. Lichter. Dynamic Organization of Nuclear Function,
2002, Cold Spring Harbor Laboratory, NY.
Talks
3-D organization of the genome in interphase nuclei of higher mammalian cells. SMSI
(State Microscopical Society of Illinois) meeting, 2001, Chicago, IL.
New computational tools to analyze the spatial distribution of nuclear entities. FOM (Focus
on Microscopy) meeting, 2004, Philadelphia, PA.Acknowledgements
This work grew to a large part because I could benefit from quite a number of people who have helped
and supported me over the course of the thesis, and everybody contributed in their own way to make it possible
for me to complete it. I had the great fortune to find two outstanding and wonderful people as my supervisors
during the time of my thesis, who I admire for their contribution to science as well as for their human spirit. I
am deeply grateful for having had the opportunity to work with both of them, Prof. Dr. Janet D. Rowley and
Prof. Dr. Peter Lichter. Thank you so much for your incredible trust in me during all this time, for your support
and interest in my research and for the truly unique opportunity to work on a thesis in Heidelberg and in
Chicago.
I wish to thank current and former members of the Rowley laboratory at the University of Chicago, for
their friendship and support; Dr. Pamela Strissel and Dr. Reiner Strick for giving me the opportunity to work in
the Rowley lab, and for their encouragement to follow my curiosity to investigate the whereabouts of MLL and
Co.; Dr. Yanming Zhang for sharing his wealth of knowledge about leukemia and translocations; Dr. Sanggyu
Lee and Dr. Run Shi for giving me insights into the SAGE-continuum and their never ending patience to listen
to my ideas; Miao Sun for the computer SAGE tag searches; my students Emily Carpenter, Marissa Encinosa
and Harshal Dave, who I tremendously enjoyed training over the summers; and my friends Dr. Yuri Kobzev,
Susanne Borgers, Mary Beth Neilly, Nimanthi Jayathilaka, Neelmini (Nimmi) Emmanuel, Heidrun (Heidi)
Gerr, Loretta Li and Michelle Nassin.
The Rowley lab is located in a great environment of other research groups with terrific people right next
door, the Le Beau- and the Olopade-labs. I owe a large gratitude to many of the members of these labs for all
their help I was fortunate to receive. I want to thank in particular Dr. James Fackenthal and Elizabeth (Liz)
Davis. Both helped me with their wisdom and experience, always available, never tired to answer my
thousands of questions throughout the years. Special thanks also to Aparna Palakodeti for sharing her expertise
in cell synchronization, Yanwen Jiang for his math skills, and Dr. Katrin Carlson from the Cytogenetics lab for
teaching me the identification of human chromosomes. I am also grateful to Dr. Tatyana Grushko, Dr. Gleb
Baida, Dr. Lucy Godley, Dr. Isabelle Lucas, Anthony (Tony) Fernald, Lise Sveen, Fitsum Hagos, Johnnie Byrd
and Gene Lee. Without them I would have had a less joyous time.
I want to thank Dr. Michelle Le Beau and Dr. Janis Burkhardt especially for their help to get me focused
during the time my laboratory-supervisors left the University and their generosity and encouragement to seek
skilled advice from members of their groups.
Thanks to Dr. Vytas Bindokas, Shirley Bond, and Julie Auger for their help to master many great
machines in the Core Facilities of the University of Chicago; Rafael Espinosa and Ian Miller for support in
computer and ftp-server related issues; Shanda Maaskant, Larry Hill and Tracie DeMack for helping in
administrative aspects; Gloria Davis and Jade Giacobbe for all the food, coffee and clean labware that make the
lab run. It was an enrichment to have contact with Dr. Antje Fischer, who provided material from Chinese
muntjac, and Dr. Jörg Volkland, who helped me to obtain tissue from roedeer.
I want to thank the Lichter-lab at the DKFZ in Heidelberg so much for making me feel welcomed each
time I came to give a progress report, to complete critical experiments or to learn new techniques. This was a
very important part of my thesis. I am also grateful to Dr. Stefan Lampel for starting the muntjac project and
teaching me the basics of 3D-FISH. Millions of thanks to Dr. Markus Scheuermann for his friendship, our
collaboration and all the interest and excitement for my work, and Dr. Antoinetta Mincheva for her experience
and skills in FISH.
Very special thanks to the miracle worker Juntao Gao from the Eils Group, without whom the 3D world
of the interphase nucleus could not have been mapped so precisely. He played an important role in helping me
complete the work.
I could not think of a better family, than mine, my parents, Marianne and Volkmar, and my three sisters,
Annette, Sabine and Tanja, who are there for me, always, and especially my great children Johannes and Julie,
and Marcus, my wonderful friend, partner and husband, for his encouragement, belief in me, computer support,
and cheerful optimism, from which I benefit every day.
Thank you.Table of Contents:
1. INTRODUCTION................................................................................ 1
1.1. The mammalian nucleus..................................................................................... 1
1.1.1. Positions of chromosomes within the nucleus................................................. 3
1.1.2. Movements of chromosomes within the nucleus............................................. 4
1.2. Chromosomal territories..................................................................................... 5
1.3. The interchromosomal domain (ICD) compartment model............................ 7
1.4. The position of genes in the nucleus affects their function............................... 8
1.5. 3D localization of chromosomes and their genes in the nucleus
– the role of gene density..................................................................................... 8
1.6. The evolution of the mammalian genome - the genus Muntiacus................... 10
1.7. The tandem fusion theory.................................................................................... 12
1.8. Differences and shared principles that determine gene localization
among mammalian species.................................................................................. 14
1.9. Chromosomal translocations............................................................................... 16
1.10. Double strand breaks are involved in translocation events.............................. 19
1.10.1. V(D)J recombination