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DTSTART;TZID=Europe/Stockholm:20250114T150000
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DTSTAMP:20260421T192123
CREATED:20241219T095942Z
LAST-MODIFIED:20250109T104128Z
UID:177922-1736866800-1736870400@www.scilifelab.se
SUMMARY:Transcription Regulation\, One Molecule at a Time
DESCRIPTION:Speaker: Arnaud Krebs\, PhD\, EMBL Heidelberg \n\n\n\nAbstract\n\n\n\nTranscription factors (TFs) bind at cis-regulatory elements (CREs) such as enhancers and promoters to activate transcription. In higher eukaryotes\, chromatin presents a physical barrier that needs to be overcomedby TFs to access their DNA recognition motifs and activate transcription. Cooperativity is assumed to be a key mechanism for TFs to outcompete nucleosomes. Yet\, the contribution of individual TFs to chromatin accessibility at CREs\, and how their functions are assembled is currently not understood.   \n\n\n\nCurrent bulk assays used to map TF occupancy average binding events arising from millions of individual cells\, not informing on the potential cooperativity and the antagonisms that organize their binding at CRE. To move beyond this boundary\, we developed Single Molecule Footprinting (SMF) to quantify the binding of TFs at mouse regulatory regions.  The method allows to simultaneously measure the occurrence of multiple TFs\, nucleosomes and DNA methylation on individual molecules genome-wide.  \n\n\n\nI will illustrate how we leveraged this new layer of information to understand mechanisms of TF cooperativity and dissect the basic assembly rules used by TFs to open chromatin at CREs. Moreover\, I will elaborate on our efforts to leverage long-read sequencing to study the coordination of regulatory processes between enhancers and promoters that regulate the same gene. \n\n\n\nRelevant publications: \n\n\n\nSingle-molecule footprinting identifies context-dependent regulation of enhancers by DNA methylation. Kreibich E\,. et al. Molecular Cell. 2023 \n\n\n\nSingle molecule occupancy patterns of transcription factors reveal determinants of cooperative binding in vivo; Sönmezer\, C\, et al. Molecular Cell. 2021. \n\n\n\nStudying transcription factor function in the genome at molecular resolution. Krebs\, AR\, Trends in Genetics. 2021 \n\n\n\nBiography\n\n\n\nArnaud Krebs runs a lab in functional genomics at EMBL with a focus on the study of gene regulation mechanism.  \n\n\n\nIn his lab a new method was developed to perform single-molecule footprinting (SMF)\, a methodology to quantify protein–DNA contacts at the level of single DNA molecules and they were able to quantify the patterns of occupancy of transcription factors. The lab also revealed principles about the combinatorial action of transcription factors at regulatory regions. Using their single-molecule footprinting approach they identified that the binding of TFs on individual DNA molecules is influenced by DNA methylation.  \n\n\n\nThe lab has a strong reputation to study the multiple layers of regulatory information by developing high-throughput experimental and computational strategies. \n\n\n\n \n\n\n\nShort biosketch\n\n\n\n\nERC CoG investigator 2023.\n\n\n\nSince January 2018 – Group leader at EMBL Genome Biology Unit.\n\n\n\nAmbizione independent fellow at the FMI\, Basel\, Switzerland. \n\n\n\nPostdoctoral research at the Friedrich Miescher Institute for Biomedical Research (FMI)\, Basel\, Switzerland. Advisor: Dirk Schübeler\n\n\n\nPhD\, 2011\, IGBMC\, Strasbourg\, France. Advisor: Laszlo Tora\n\n\n\nMasters in Molecular Biology (Uni Nancy\, France) and Bioinformatics (Uni Pierre and Marie Curie\, Paris)\n\n\n\n\n\n\n\n\nThe seminar will be followed by a fika (coffee break) where young scientists (PhD students and postdocs) can meet the speaker and ask questions about the seminar and his scientific career. \n\n\n\nRegister for Meet the Speaker fika
URL:https://www.scilifelab.se/event/transcription-regulation-one-molecule-at-a-time/
LOCATION:Air&Fire\, SciLifeLab Stockholm\, Tomtebodavägen 23A\, Solna\, Sweden
CATEGORIES:Event
ATTACH;FMTTYPE=image/jpeg:https://www.scilifelab.se/wp-content/uploads/2023/10/Campus-solna-seminar-picture.jpg
ORGANIZER;CN="Spotlight Seminar Series":MAILTO:events@scilifelab.se
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