Our Research
We aim to understand fundamental principles of gene regulation.
Regulatory mechanisms that modify chromatin structure are an integral part of this process. These include reversible modification of histones, DNA methylation and chromatin remodeling. How these function, crosstalk to transcription factors and depend on the underlying DNA sequence is of particular interest for us.
We want to understand how chromatin states are generated and how they are involved in the information flow towards transcription. Mammalian cells serve as model system enabling us to combine molecular biology approaches with genome-wide experimental readouts. We generate comprehensive datasets of the genomic distribution of epigenome variables in combination with targeted analysis of individual sequences. From the resulting datasets we derive and test regulatory models with the ultimate goal to implement epigenetic regulation into current models of transcriptional regulation.
selected publications:
Evidence that direct inhibition of transcription factor binding is the prevailing mode of gene and repeat repression by DNA methylation
Sebastian Kaluscha, Silvia Domcke, Christiane Wirbelauer, Michael B Stadler, Sevi Durdu, Lukas Burger, Dirk Schübeler (2022)
Nat Genet. 2022 Dec;54(12):1895-1906
BANP opens chromatin and activates CpG-island-regulated genes
Ralph S. Grand*, Lukas Burger*, Cathrin Gräwe, Alicia K. Michael, Luke Isbel, Daniel Hess, Leslie Hoerner, Vytautas Iesmantavicius, Sevi Durdu, Marco Pregnolato, Arnaud R. Krebs, Sébastien A. Smallwood, Nicolas Thomä, Michiel Vermeulen & Dirk Schübeler (2021)
Nature 596, pages 133-137
Mammalian SWI/SNF continuously restores local accessibility to chromatin
Mario Iurlaro, Michael B. Stadler, Francesca Masoni, Zainab Jagani, Giorgio G. Galli and Dirk Schübeler (2021)
Nature Genetics 53, pages 279-287
Mechanisms of OCT4-SOX2 motif readout on nucleosomes
Alicia K. Michael*, Ralph S. Grand*, Luke Isbel*, Simone Cavadini, Zuzanna Kozicka, Georg Kempf, Richard D. Bunker, Andreas D. Schenk, Alexandra Graff-Meyer, Ganesh R. Pathare, Joscha Weiss, Syota Matsumoto, Lukas Burger, Dirk Schübeler and Nicolas H. Thomä (2020)
Science, Vol. 368, Issue 6498, pp. 1460-1465
A genome-scale map of DNA methylation turnover identifies site-specific dependencies of DNMT and TET activity
Paul Adrian Ginno, Dimos Gaidatzis, Angelika Feldmann, Leslie Hoerner, Dilek Imanci, Lukas Burger, Frederic Zilbermann, Antoine H. F. M. Peters, Frank Edenhofer, Sebastien Smallwood, Arnaud Krebs & Dirk Schübeler (2020)
Nature Communications 11, 2680
Mammalian ISWI and SWI/SNF selectively mediate binding of distinct transcription factors
Barisic D, Stadler MB, Iurlaro M, Schübeler D (2019)
Nature. 2019 Apr 17
CG dinucleotides enhance promoter activity independent of DNA methylation
Hartl D, Krebs AR, Grand RS, Baubec T, Isbel L, Wirbelauer C, Burger L, Schübeler D (2019)
Genome Res. 2019 Apr;29(4):554-563
Non-mendelian inheritance in mammals is highly constrained
Isbel L, Schübeler D (2018)
Cell. 2018 Nov 15;175(5):1179-1181
Cell cycle-resolved chromatin proteomics reveals the extent of mitotic preservation of the genomic regulatory landscape
PA Ginno, L Burger, J Seebacher, V Iesmantavicius, D Schübeler
Nature Communications 9 (1), 4048
Binding of high mobility group A proteins to the mammalian genome occurs as a function of AT-content
DF Colombo, L Burger, T Baubec, D Schübeler
PLoS Genetics 13 (12), e1007102
Genomic profiling of DNA methyltransferases reveals a role for DNMT3B in genic methylation
T Baubec, DF Colombo, C Wirbelauer, J Schmidt, L Burger, AR Krebs, A Akalin, D Schübeler
Nature 520 (7546), 243
Methylation-dependent and-independent genomic targeting principles of the MBD protein family
T Baubec, R Ivánek, F Lienert, D Schübeler
Cell 153 (2), 480-492
Competition between DNA methylation and transcription factors determines binding of NRF1
S Domcke, AF Bardet, PA Ginno, D Hartl, L Burger, D Schübeler
Nature 528 (7583), 575
Transcription factor occupancy can mediate active turnover of DNA methylation at regulatory regions
A Feldmann, R Ivanek, R Murr, D Gaidatzis, L Burger, D Schübeler
PLoS Genetics 9 (12), e1003994
DNA-binding factors shape the mouse methylome at distal regulatory regions
MB Stadler, R Murr, L Burger, R Ivanek, F Lienert, A Schöler, E van Nimwegen, C Wirbelauer, EJ Oakeley, D Gaidatzis, VK Tiwari, D Schübeler
Nature 480, 490–495
Genome-wide single-molecule footprinting reveals high RNA polymerase II turnover at paused promoters
AR Krebs, D Imanci, L Hoerner, D Gaidatzis, L Burger, D Schübeler
Molecular Cell 67 (3), 411-422. e4
High-throughput engineering of a mammalian genome reveals building principles of methylation states at CG rich regions
AR Krebs, S Dessus-Babus, L Burger, D Schübeler
eLife 3, e04094
Identification of genetic elements that autonomously determine DNA methylation states
F Lienert, C Wirbelauer, I Som, A Dean, F Mohn, D Schübeler
Nature Genetics 43 (11), 1091
Determinants and dynamics of genome accessibility
Bell O, Tiwari VK, Thomä NH, Schübeler D (2011)
Nat Rev Genet. 12:554-64
DNA accessibility discriminates sites of PcG repression, H4K16 acetylation and replication initiation throughout the genome
Bell O, Schwaiger M, Oakeley EJ, Lienert F, Beisel C, Stadler MB, Schübeler D (2010)
Nat Struct Mol Biol. 17:894-900
Polycomb targets and de novo DNA methylation define restriction and potential of neuronal progenitors
Mohn F, Weber M, Rebhan M, Roloff TC, Richter J, Stadler MB, Bibel M, Schübeler D (2008)
Molecular Cell. 30:755-766
Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome
Weber M, Hellmann I, Stadler MB, Ramos L, Pääbo S, Rebhan M, Schübeler D (2007)
Nature Genet. 39:457-466
Chromosome-wide and promoter-specific analyses reveal sites of differential DNA methylation in normal and transformed human cells
Weber M, Davies J, Wittig D, Oakeley E, Haase M, Lam WL, Schübeler D (2005)
Nature Genet. 37:853-862