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SUMMARY:Genome-wide analysis of protein-DNA interactions - Professor Jussi
  Taipale\, Herchel Smith Professor of Biochemistry
DTSTART:20171120T170000Z
DTEND:20171120T180000Z
UID:TALK95305@talks.cam.ac.uk
CONTACT:45561
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 in the presence and absence of nucleosomes\, using multiple d
 ifferent methods. Our findings indicate that DNA commonly mediates interac
 tions between TFs\, and that dimer formation results in changes in the bin
 ding preferences of TFs. We also found that CpG methylation has a major im
 pact on TF binding. Binding of most major classes of TFs\, including bHLH\
 , bZIP\, and ETS is inhibited by mCpG. In contrast\, TFs that prefer to bi
 nd to methylated DNA mainly represent homeodomain\, POU and NFAT proteins\
 , and are enriched in TFs with central roles in embryonic and organismal d
 evelopment. Despite the extensive knowledge of TF binding preferences\, re
 ading the regulatory code remains a challenge. To address this\, we have b
 egun to identify the sources of this problem by performing several experim
 ents that bridge the gap between in vivo analyses such as ChIP-seq and in 
 vitro studies such as HT-SELEX. A binding model that is required to unders
 tand binding of TFs to the genome\, which incorporates information about c
 ellular TF activity\, protein-protein interactions induced by DNA\, and in
 heritance of epigenetic states across cell division will be discussed.
LOCATION:Department of Biochemistry\, Sanger Building Jean Thomas Lecture 
 Theatre
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