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DTSTAMP:20260424T074454Z
UID:1741698000@ist.ac.at
DTSTART:20250311T140000
DTEND:20250311T150000
DESCRIPTION:Speaker: Ralph Grand\nhosted by Alicia Michael\nAbstract: Cell 
 viability depends on the expression of common essential genes (CEGs) that 
 encode for fundamental cellular processes such as metabolism. The level of
  CEG expression is tightly controlled across cell types and developmental 
 stages\, with dysregulation linked to disease\, yet\, the mechanisms gover
 ning CEG regulation remain unclear. CpG island (CGI) promoters\, the most 
 prevalent cis-regulatory element in the mammalian genome\, drive CEG expre
 ssion. They contain assemblies of transcription factor (TF) binding sites 
 and the highest TF binding density among promoters\, leading to a model wh
 ere CGIs activity is regulated by the combinatorial action of multiple TFs
 . This makes CGIs an intriguing model to study how TFs cooperate to open c
 hromatin and activate genes\, including CEGs.To address this\, we investig
 ated five essential TFs that co-bind extensively at CEG promoters in murin
 e stem cells. To dissect their regulatory roles\, we used individual and c
 ombinatorial inducible degron systems\, enabling to map the primary effect
 s on gene expression and chromatin accessibility following rapid TF deplet
 ion and recovery. This identified TFs that can drive chromatin opening and
  transcriptional activation\, while others regulate gene expression withou
 t altering chromatin state. The ability to open chromatin was promoter-spe
 cific and could not be compensated for by additional co-bound TFs. Further
 more\, this pioneer activity facilitated the recruitment of co-bound TFs\,
  allowing us to reconstruct the hierarchical binding events necessary for 
 CGI promoter function. We found some genes where TF cooperativity tuned ge
 ne expression\, both enhancing and repressing activity\, however\, the maj
 ority of genes were predominantly controlled by individual TFs. Our study 
 provides new insights into CEG regulation\, revealing that CGI promoters a
 re continually pioneered by master TFs that organize chromatin\, define bi
 nding hierarchies\, and drive gene activation.
LOCATION:Moonstone Ground Floor Seminar Room E\, ISTA
ORGANIZER:alicia.michael@ista.ac.at 
SUMMARY:Ralph Grand: Essential genes are pioneered and activated by master 
 transcription factors
URL:https://talks-calendar.ista.ac.at/events/5598
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