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SUMMARY:Genome-wide analysis of protein-DNA interactions - Prof. Jussi Tai
 pale\; Herchel Smith Professor of Biochemistry\, Department of Biochemistr
 y\, University of Cambridge
DTSTART:20180312T130000Z
DTEND:20180312T140000Z
UID:TALK98383@talks.cam.ac.uk
CONTACT:Bobbie Claxton
DESCRIPTION:Understanding the information encoded in the human genome requ
 ires two genetic codes\, the first code specifies how mRNA sequence is con
 verted to protein sequence\, and the second code determines where and when
  the mRNAs are expressed. Although the proteins that read the second\, reg
 ulatory code – transcription factors (TFs) – have been largely identif
 ied\, the code is poorly understood as it is not known which sequences TFs
  can bind in the genome. To understand the regulatory code\, we have analy
 zed the sequence-specific binding of TFs to unmodified and epigenetically 
 modified DNA using multiple different methods. Our findings indicate that 
 DNA commonly mediates interactions between TFs\, and that dimer formation 
 results in changes in the binding preferences of TFs. We also found that C
 pG methylation has a major impact on TF binding. Binding of most major cla
 sses of TFs\, including bHLH\, bZIP\, and ETS is inhibited by mCpG. In con
 trast\, TFs that prefer to bind to methylated DNA mainly represent homeodo
 main\, POU and NFAT proteins\, and are enriched in TFs with central roles 
 in embryonic and organismal development. Despite the extensive knowledge o
 f TF binding preferences\, reading the regulatory code remains a challenge
 . To address this\, we have begun to identify the sources of this problem 
 by performing several experiments that bridge the gap between in vivo anal
 yses such as ChIP-seq and in vitro studies such as SELEX. These approaches
  include analysis of TF binding in the presence of the nucleosome\, determ
 ining DNA-binding activities of all TFs from distinct cell types\, and det
 ermining transcriptional activities of TF motifs in vivo. A binding model 
 that is required to understand binding of TFs to the genome\, which incorp
 orates information about cellular TF activity\, protein-protein interactio
 ns induced by DNA\, and inheritance of epigenetic states across cell divis
 ion will be discussed.
LOCATION:Babraham - The Cambridge Building\; Kings Hedges Room
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