BEGIN:VCALENDAR
VERSION:2.0
PRODID:-//Talks.cam//talks.cam.ac.uk//
X-WR-CALNAME:Talks.cam
BEGIN:VEVENT
SUMMARY:Transcriptional Lego: Predictable control of gene expression by ma
 nipulating promoter building blocks - Eran Segal\, Weizmann Institute of S
 cience
DTSTART:20100916T120000Z
DTEND:20100916T130000Z
UID:TALK21492@talks.cam.ac.uk
CONTACT:Katrien Van Look
DESCRIPTION:The ability to control the timing and levels at which genes ar
 e expressed is key to most biological processes. Although we know the sequ
 ence preferences of key players in this process\, we are still far from un
 derstanding how these elements combine within regulatory sequences to enco
 de the transcriptional outcome. Based on our theoretical analyses\, we dev
 ised hypotheses regarding the effect that different nucleosome disfavoring
  sequences that vary in length\, composition\, and distance from transcrip
 tion factor binding sites\, will have on the transcriptional outcome. To s
 ystematically test these hypotheses\, we designed and synthesized ~80 prom
 oter sequences\, and fused each promoter to a fluorescent reporter\, resul
 ting in the largest library of designed promoter variants to date. Our res
 ults show that by manipulating either or both transcription factor binding
  sites and nucleosome disfavoring sequences in the vicinity of the site\, 
 we can tune expression levels in a predictable manner. Importantly\, seque
 nce changes that only alter nucleosome disfavoring sequences result in eff
 ects on expression comparable in magnitude to those that result from chang
 es to transcription factor binding sites. In fact\, compared to binding si
 te changes\, alterations of nucleosome disfavoring sequences likely yield 
 more gradual changes in expression levels\, and thus offer means to fine-t
 une gene expression with high resolution. These results have intriguing im
 plications for evolution of gene expression\, suggesting that sequence cha
 nges that alter the DNA-encoded nucleosome organization may provide an eff
 icient genetic mechanism by which genomes may evolve and fine-tune gene ex
 pression. Overall\, our results bring us a step closer towards understandi
 ng the role of various promoter elements and their combined effects on tra
 nscription\, and suggest that directed design of promoter sequences that y
 ield pre-specified expression patterns may be within reach.
LOCATION:Cancer Research UK Cambridge Research Institute\, Lecture Theatre
END:VEVENT
END:VCALENDAR