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Structural biology of mammalian transcription regulation

Total Cost €


EC-Contrib. €






Project "TRANSREGULON" data sheet

The following table provides information about the project.


Organization address
city: Munich
postcode: 80539

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Total cost 2˙496˙250 €
 EC max contribution 2˙496˙250 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-AdG
 Funding Scheme ERC-ADG
 Starting year 2016
 Duration (year-month-day) from 2016-07-01   to  2021-06-30


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 


 Project objective

The regulation of gene transcription by RNA polymerase (Pol) II underlies cell differentiation and organism development, and its dysregulation causes many cancers. Transcription regulation occurs during initiation, when Pol II assembles with initiation factors on promoter DNA, but also during mRNA chain elongation, when Pol II pauses near the promoter before it restarts upon activation. Our previous ERC Advanced Grant ‘TRANSIT’ enabled us to provide molecular insights into yeast Pol II initiation and its regulation by the Mediator coactivator complex (Plaschka et al., Nature 2015; Sainsbury et al., Nature 2012, Lariviere et al, Nature 2012). Here, with our new proposal ‘TRANSREGULON’ we wish to open a new frontier and provide the structural basis for mammalian Pol II regulation during elongation. We will use an integrated structural biology approach combining X-ray crystallography, cryo-electron microscopy, and crosslinking, to obtain the first atomic structure of a mammalian Pol II enzyme (aim 1), the structure of the negative elongation factor NELF (aim 2), which is required for promoter-proximal pausing by mammalian Pol II, and the threedimensional architecture of the promoter-proximally paused Pol II complex (aim 3) containing the multiprotein pausing factors NELF and DSIF, and eventually also the pause release factor p-TEFb. This ground-breaking work will make the transition from yeast to human structural biology of transcription, will provide the molecular basis for a central mechanism of cellular regulation, and will advance structural biology methods for dissecting large and transient mammalian multicomponent complexes.


year authors and title journal last update
List of publications.
2019 Gert-Jan Hendriks, Lisa A. Jung, Anton J. M. Larsson, Michael Lidschreiber, Oscar Andersson Forsman, Katja Lidschreiber, Patrick Cramer, Rickard Sandberg
NASC-seq monitors RNA synthesis in single cells
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-019-11028-9
Nature Communications 10/1 2019-08-29
2019 Salma Sohrabi-Jahromi, Katharina B Hofmann, Andrea Boltendahl, Christian Roth, Saskia Gressel, Carlo Baejen, Johannes Soeding, Patrick Cramer
Transcriptome maps of general eukaryotic RNA degradation factors
published pages: , ISSN: 2050-084X, DOI: 10.7554/elife.47040
eLife 8 2019-08-29
2017 Sofia Battaglia, Michael Lidschreiber, Carlo Baejen, Phillipp Torkler, Seychelle M Vos, Patrick Cramer
RNA-dependent chromatin association of transcription elongation factors and Pol II CTD kinases
published pages: , ISSN: 2050-084X, DOI: 10.7554/eLife.25637
eLife 6 2019-06-13
2017 Youwei Xu, Carrie Bernecky, Chung-Tien Lee, Kerstin C. Maier, Björn Schwalb, Dimitry Tegunov, Jürgen M. Plitzko, Henning Urlaub, Patrick Cramer
Architecture of the RNA polymerase II-Paf1C-TFIIS transcription elongation complex
published pages: 15741, ISSN: 2041-1723, DOI: 10.1038/ncomms15741
Nature Communications 8 2019-06-13
2017 Saskia Gressel, Björn Schwalb, Tim Michael Decker, Weihua Qin, Heinrich Leonhardt, Dirk Eick, Patrick Cramer
CDK9-dependent RNA polymerase II pausing controls transcription initiation
published pages: , ISSN: 2050-084X, DOI: 10.7554/eLife.29736
eLife 6 2019-06-13
2017 Margaux Michel, Carina Demel, Benedikt Zacher, Björn Schwalb, Stefan Krebs, Helmut Blum, Julien Gagneur, Patrick Cramer
TT‐seq captures enhancer landscapes immediately after T‐cell stimulation
published pages: 920, ISSN: 1744-4292, DOI: 10.15252/msb.20167507
Molecular Systems Biology 13/3 2019-06-13
2017 Benedikt Zacher, Margaux Michel, Björn Schwalb, Patrick Cramer, Achim Tresch, Julien Gagneur
Accurate Promoter and Enhancer Identification in 127 ENCODE and Roadmap Epigenomics Cell Types and Tissues by GenoSTAN
published pages: e0169249, ISSN: 1932-6203, DOI: 10.1371/journal.pone.0169249
PLOS ONE 12/1 2019-06-13
2017 Stefano Malvezzi, Lucas Farnung, Claudia M. N. Aloisi, Todor Angelov, Patrick Cramer, Shana J. Sturla
Mechanism of RNA polymerase II stalling by DNA alkylation
published pages: 12172-12177, ISSN: 0027-8424, DOI: 10.1073/pnas.1706592114
Proceedings of the National Academy of Sciences 114/46 2019-06-13
2017 Ameet Shetty, Scott P. Kallgren, Carina Demel, Kerstin C. Maier, Dan Spatt, Burak H. Alver, Patrick Cramer, Peter J. Park, Fred Winston
Spt5 Plays Vital Roles in the Control of Sense and Antisense Transcription Elongation
published pages: 77-88.e5, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2017.02.023
Molecular Cell 66/1 2019-03-18
2017 Hauke S. Hillen, Andrey V. Parshin, Karen Agaronyan, Yaroslav I. Morozov, James J. Graber, Aleksandar Chernev, Kathrin Schwinghammer, Henning Urlaub, Michael Anikin, Patrick Cramer, Dmitry Temiakov
Mechanism of Transcription Anti-termination in Human Mitochondria
published pages: 1082-1093.e13, ISSN: 0092-8674, DOI: 10.1016/j.cell.2017.09.035
Cell 171/5 2019-03-18
2017 Lucas Farnung, Seychelle M. Vos, Christoph Wigge, Patrick Cramer
Nucleosome–Chd1 structure and implications for chromatin remodelling
published pages: 539-542, ISSN: 0028-0836, DOI: 10.1038/nature24046
Nature 550/7677 2019-03-18
2017 Patrick Cramer
Structural Molecular Biology—A Personal Reflection on the Occasion of John Kendrew\'s 100th Birthday
published pages: 2603-2610, ISSN: 0022-2836, DOI: 10.1016/j.jmb.2017.05.007
Journal of Molecular Biology 429/17 2019-03-18
2017 S. Schilbach, M. Hantsche, D. Tegunov, C. Dienemann, C. Wigge, H. Urlaub, P. Cramer
Structures of transcription pre-initiation complex with TFIIH and Mediator
published pages: , ISSN: 0028-0836, DOI: 10.1038/nature24282
Nature 2019-03-18
2018 Seychelle M. Vos, Lucas Farnung, Henning Urlaub, Patrick Cramer
Structure of paused transcription complex Pol II–DSIF–NELF
published pages: 601-606, ISSN: 0028-0836, DOI: 10.1038/s41586-018-0442-2
Nature 560/7720 2019-03-18
2017 R. Kohler, R. A. Mooney, D. J. Mills, R. Landick, P. Cramer
Architecture of a transcribing-translating expressome
published pages: 194-197, ISSN: 0036-8075, DOI: 10.1126/science.aal3059
Science 356/6334 2019-03-18
2017 Christoph Engel, Tobias Gubbey, Simon Neyer, Sarah Sainsbury, Christiane Oberthuer, Carlo Baejen, Carrie Bernecky, Patrick Cramer
Structural Basis of RNA Polymerase I Transcription Initiation
published pages: 120-131.e22, ISSN: 0092-8674, DOI: 10.1016/j.cell.2017.03.003
Cell 169/1 2019-03-18
2017 Carlo Baejen, Jessica Andreani, Phillipp Torkler, Sofia Battaglia, Bjoern Schwalb, Michael Lidschreiber, Kerstin C. Maier, Andrea Boltendahl, Petra Rus, Stephanie Esslinger, Johannes Söding, Patrick Cramer
Genome-wide Analysis of RNA Polymerase II Termination at Protein-Coding Genes
published pages: 38-49.e6, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2017.02.009
Molecular Cell 66/1 2019-03-18
2018 Lucas Farnung, Seychelle M. Vos, Patrick Cramer
Structure of transcribing RNA polymerase II-nucleosome complex
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-07870-y
Nature Communications 9/1 2019-03-18
2017 Hauke S. Hillen, Yaroslav I. Morozov, Azadeh Sarfallah, Dmitry Temiakov, Patrick Cramer
Structural Basis of Mitochondrial Transcription Initiation
published pages: 1072-1081.e10, ISSN: 0092-8674, DOI: 10.1016/j.cell.2017.10.036
Cell 171/5 2019-03-18
2017 Merle Hantsche, Patrick Cramer
Conserved RNA polymerase II initiation complex structure
published pages: 17-22, ISSN: 0959-440X, DOI: 10.1016/
Current Opinion in Structural Biology 47 2019-03-18
2019 Jan Jakub Żylicz, Aurélie Bousard, Kristina Žumer, Francois Dossin, Eusra Mohammad, Simão Teixeira da Rocha, Björn Schwalb, Laurène Syx, Florent Dingli, Damarys Loew, Patrick Cramer, Edith Heard
The Implication of Early Chromatin Changes in X Chromosome Inactivation
published pages: 182-197.e23, ISSN: 0092-8674, DOI: 10.1016/j.cell.2018.11.041
Cell 176/1-2 2019-03-18
2018 Michael Lidschreiber, Ashley D Easter, Sofia Battaglia, Juan B Rodríguez-Molina, Ana Casañal, Manuel Carminati, Carlo Baejen, Pawel Grzechnik, Kerstin C Maier, Patrick Cramer, Lori A Passmore
The APT complex is involved in non-coding RNA transcription and is distinct from CPF
published pages: , ISSN: 0305-1048, DOI: 10.1093/nar/gky845
Nucleic Acids Research 2019-03-18
2018 Seychelle M. Vos, Lucas Farnung, Marc Boehning, Christoph Wigge, Andreas Linden, Henning Urlaub, Patrick Cramer
Structure of activated transcription complex Pol II–DSIF–PAF–SPT6
published pages: 607-612, ISSN: 0028-0836, DOI: 10.1038/s41586-018-0440-4
Nature 560/7720 2019-09-05
2019 Goran Kokic, Aleksandar Chernev, Dimitry Tegunov, Christian Dienemann, Henning Urlaub, Patrick Cramer
Structural basis of TFIIH activation for nucleotide excision repair
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-019-10745-5
Nature Communications 10/1 2019-08-29
2019 Leonhard Wachutka, Livia Caizzi, Julien Gagneur, Patrick Cramer
Global donor and acceptor splicing site kinetics in human cells
published pages: , ISSN: 2050-084X, DOI: 10.7554/elife.45056
eLife 8 2019-08-29
2017 Carrie Bernecky, Jürgen M Plitzko, Patrick Cramer
Structure of a transcribing RNA polymerase II–DSIF complex reveals a multidentate DNA–RNA clamp
published pages: 809-815, ISSN: 1545-9993, DOI: 10.1038/nsmb.3465
Nature Structural & Molecular Biology 24/10 2019-09-05

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