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SUMMARY:What is the epigenetic landscape of the vertebrate kinetochore? - 
 Prof William Earnshaw\, Wellcome Trust Centre for Cell Biology\, Universit
 y of Edinburgh
DTSTART:20130206T120000Z
DTEND:20130206T130000Z
UID:TALK43127@talks.cam.ac.uk
CONTACT:Dr Ireena Dutta
DESCRIPTION:The regional kinetochores of vertebrate chromosomes are propag
 ated stably over thousands of generations. Kinetochores assemble on prefer
 red DNA sequences\, but there is no absolute sequence requirement. This\, 
 and studies of highly unusual human stable dicentric chromosomes have led 
 to the hypothesis that kinetochore assembly has an epigenetic component. T
 his was supported by the discovery that CENP-A\, a critical determinant th
 at marks the site of kinetochore assembly\, is a specialized centromeric H
 3 family member. Thus kinetochores are built on a platform of specialized 
 chromatin. I will discuss work in which we use a synthetic artificial chro
 mosome that was designed to allow targeting of chimeric molecules into the
  kinetochore chromatin for “epigenetic engineering” of that chromatin.
  This approach enables us to modify one single kinetochore within a human 
 cell\, whilst leaving all other kinetochores untouched and fully functiona
 l. Our aim is to identify the suite of chromatin posttranslational modific
 ations that is conducive to kinetochore assembly and maintenance\, and to 
 determine the functional consequences when these modifications are removed
  or altered. Our data have thus far uncovered a remarkable plasticity of f
 unctional centromeres in vivo. Kinetochores can tolerate profound changes 
 in their chromatin environment\, but they appear to be critically sensitiv
 e to the level of centromeric transcription.  
LOCATION:Sackler Lecture Theatre\, CIMR\,  Level 7
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