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SUMMARY:Principles of Dynamic gene regulation in mammals\, hosted by Sarah
  Teichmann - Ido Amit\, Weizman Institute\, Israel
DTSTART:20121019T133000Z
DTEND:20121019T143000Z
UID:TALK40743@talks.cam.ac.uk
CONTACT:Dr Tennie Videler
DESCRIPTION:Dynamic binding of transcription factors to DNA elements speci
 fies gene expression and cell fate\, in both normal physiology and disease
 . To date\, our understanding of mammalian gene regulation has been hamper
 ed by the difficulty of directly measuring in vivo binding of large number
 s of transcription factors to DNA. Here\, we develop a high-throughput ind
 exed Chromatin ImmunoPrecipitation (iChIP) method coupled to massively par
 allel sequencing to systematically map protein-DNA interactions. We apply 
 iChIP to reconstruct the physical regulatory landscape of a mammalian cell
 \, by building genome-wide binding maps for 41 transcription factors (TFs)
  and chromatin marks at four time points following stimulation of primary 
 dendritic cells (DCs) with pathogen components. Using over 200\,000 TF-DNA
  interactions in these maps\, we derive the first comprehensive and dynami
 c physical model of a regulatory network in a mammalian cell. Our data dem
 onstrate that transcription factors vary substantially in their binding dy
 namics\, genomic localization\, number of binding events\, and degree of i
 nteraction with other factors. Further\, many of the TFs-DNA interactions 
 are pre-established prior to stimulation and maintained in a poised state\
 , specifically on immediate early genes. We show\, that the network is com
 posed of three distinct spatial-temporal regulatory layers: Pioneers defin
 e the epigenetic state during cellular differentiation\, Primers prime\, a
 nd Transducers mediate the transcription of genes upon stimulation. These 
 factors determine the magnitude and timing of stimulus induced gene expres
 sion. By integrating these TF binding maps with RNAi perturbations\, we id
 entify two distinct regulatory schemes controlling the response. “Inflam
 matory” genes are controlled by a modular and redundant regulatory progr
 am (OR gate)\, whereas “anti-viral” response genes are controlled by a
 n all-or-none response (AND gate). Together\, these principles highlight h
 ow mammalian cells organize transcriptional networks 
LOCATION:CIMR (Cambridge Institute for Medical Research)\, Sackler Lecture
  Theater on level 7
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