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TRANSREGULON SIGNED

Structural biology of mammalian transcription regulation

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

TRANSREGULON project word cloud

Explore the words cloud of the TRANSREGULON project. It provides you a very rough idea of what is the project "TRANSREGULON" about.

transition causes breaking crosslinking electron mrna cellular proximally paused polymerase occurs frontier underlies dysregulation pauses yeast activation transit chain transcription enzyme structure human promoter 2015 wish lariviere et pausing proximal cancers gene first dissecting central molecular plaschka pause regulation near pol erc dna dsif assembles threedimensional mediator insights crystallography organism structural release nelf sainsbury transregulon obtain initiation multicomponent negative coactivator nature basis mammalian 2012 combining restarts ray al biology multiprotein architecture rna differentiation elongation microscopy cryo mechanism transient cell containing ground grant complexes enabled tefb atomic

Project "TRANSREGULON" data sheet

The following table provides information about the project.

Coordinator	MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Organization address address: HOFGARTENSTRASSE 8 city: Munich postcode: 80539 website: www.mpg.de 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

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Organization address address: HOFGARTENSTRASSE 8 city: Munich postcode: 80539 website: www.mpg.de contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	DE (Munich)	coordinator	2˙496˙250.00

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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.

Publications

List of publications.
year	authors and title	journal	last update
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, BjÃ¶rn Schwalb, Dimitry Tegunov, JÃ¼rgen 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, BjÃ¶rn 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, BjÃ¶rn Schwalb, Stefan Krebs, Helmut Blum, Julien Gagneur, Patrick Cramer TTâ€seq captures enhancer landscapes immediately after Tâ€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, BjÃ¶rn 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 Nucleosomeâ€“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 Biologyâ€”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 IIâ€“DSIFâ€“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 SÃ¶ding, 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/j.sbi.2017.03.013	Current Opinion in Structural Biology 47	2019-03-18
2019	Jan Jakub Å»ylicz, AurÃ©lie Bousard, Kristina Å½umer, Francois Dossin, Eusra Mohammad, SimÃ£o Teixeira da Rocha, BjÃ¶rn Schwalb, LaurÃ¨ne 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 RodrÃguez-Molina, Ana CasaÃ±al, 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 IIâ€“DSIFâ€“PAFâ€“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, JÃ¼rgen M Plitzko, Patrick Cramer Structure of a transcribing RNA polymerase IIâ€“DSIF complex reveals a multidentate DNAâ€“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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