BEGIN:VCALENDAR
VERSION:2.0
PRODID:-//Memento EPFL//
BEGIN:VEVENT
SUMMARY:EPFL BioE Talks SERIES  "Cooperativity and Antagonisms in Transcri
 ption Regulation"
DTSTART:20231211T160000
DTEND:20231211T170000
DTSTAMP:20260925T090717Z
UID:31baa03189934688f84924c3be00a43269627dc8b587dbdfed1127da
CATEGORIES:Conferences - Seminars
DESCRIPTION:Arnaud Krebs\, Ph.D.\, Group Leader\, Genome Biology Unit\, EM
 BL\, Heidelberg (DE)\nWEEKLY EPFL BIOE TALKS SERIES\n\nAbstract:\nTranscri
 ption factors (TFs) bind at cis-regulatory elements (CREs) such as enhance
 rs and promoters to activate transcription. In higher eukaryotes\, chromat
 in presents a physical barrier that needs to be overcome by 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 h
 ow their functions are assembled is currently not understood.\n\nCurrent b
 ulk assays used to map TF occupancy average binding events arising from mi
 llions of individual cells\, not informing on the potential cooperativity 
 and the antagonisms that organize their binding at CRE. To move beyond thi
 s boundary\, we developed Single Molecule Footprinting (SMF) to quantify t
 he binding of TFs at mouse regulatory regions. The method allows to simult
 aneously measure the occurrence of multiple TFs\, nucleosomes and DNA meth
 ylation on individual molecules genome wide. I will illustrate how we leve
 raged this new layer of information to understand mechanisms of TF coopera
 tivity and dissect the basic assembly rules used by TFs to open chromatin 
 at CREs.\n\nDetecting multiple TF binding events on single DNA molecules h
 as enabled us to determine TF co-binding frequencies in vivo and to elucid
 ate the underlying cooperative binding mechanism (Sönmezer et al\, 2021).
  We now leveraged SMF’s ability to determine the width\, and the frequen
 cy of nucleosome-free DNA occurring upon binding of individual or defined 
 combination of TFs. To infer causality in the process\, we leveraged F1 hy
 brids that contain genetic variants that disrupt TF binding motifs on indi
 vidual alleles. I will show how unbound TF motifs are exposed within 80bp-
 long stretches of accessible DNA in about one third of the cells of the po
 pulation. In contrast TF-bound molecules show longer nucleosome-free DNA (
 >100bp). Binding of individual TFs leads to chromatin accessibility in onl
 y a small fraction of cells (<20%). We find that additive and multiplicati
 ve assembly of TF chromatin-opening functions are required to explain the 
 frequency of accessibility observed at CRE\, and identify the assembly rul
 es using high-throughput genome engineering. In summary\, we identify the 
 quantitative contribution of individual TFs to chromatin accessibility and
  explain how their function are combined to form active CREs.\n\nRelevant 
 publications:\nSingle-molecule footprinting identifies context-dependent r
 egulation of enhancers by DNA methylation. Kreibich E\,. et al. Molecular 
 Cell. 2023.\nSingle molecule occupancy patterns of transcription factors r
 eveal determinants of cooperative binding in vivo\; Sönmezer\, C\, et al.
  Molecular Cell. 2021.\nStudying transcription factor function in the geno
 me at molecular resolution. Krebs\, AR\, Trends in Genetics. 2021.\n\nBio:
 \nERC CoG investigator 2023.\nSince January 2018 - Group leader at EMBL Ge
 nome Biology Unit.\nAmbizione independent fellow at the FMI\, Basel\, Swit
 zerland.\nPostdoctoral research at the Friedrich Miescher Institute for Bi
 omedical Research (FMI)\, Basel\, Switzerland. Advisor: Dirk Schübeler\nP
 hD\, 2011\, IGBMC\, Strasbourg\, France. Advisor: Laszlo Tora\nMasters in 
 Molecular Biology (Uni Nancy\, France) and Bioinformatics (Uni Pierre and 
 Marie Curie\, Paris).\n\n\nZoom link (with one-time registration for the w
 hole series) for attending remotely: https://go.epfl.ch/EPFLBioETalks\n\n\
 nInstructions for 1st-year Ph.D. students who are under EDBB’s mandatory
  seminar attendance rule:\nIF you are not attending in-person in the room\
 , please make sure to\n\n	send D. Reinhard a note before noon on seminar d
 ay\, informing that you plan to attend the talk online\, and\n	be signed i
 n on Zoom with a recognizable user name (not a pseudonym making it difficu
 lt or impossible to be identified).\n\nStudents attending the seminar in-p
 erson should collect a confirmation signature after the talk - please prin
 t your own signature sheet beforehand (71 kB pdf available for download he
 re).
LOCATION:SV 1717 https://plan.epfl.ch/?room==SV%201717 https://go.epfl.ch/
 EPFLBioETalks
STATUS:CONFIRMED
END:VEVENT
END:VCALENDAR