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SUMMARY: &quot\;Quantitative 3D-SIM imaging of chromatin domain organisati
 on&quot\;   - Dr Lothar Schermelleh\; Department of Biochemistry\, Univers
 ity of Oxford
DTSTART:20171017T120000Z
DTEND:20171017T130000Z
UID:TALK74151@talks.cam.ac.uk
CONTACT:Bobbie Claxton
DESCRIPTION:Genome function in higher eukaryotes depends on the context of
  a hierarchical chromatin organisation. Recent genome-wide contact probabi
 lity (HiC) maps have highlighted distinct ~1Mb sized topologically associa
 ted domains (TADs) that may serve as fundamental subunits important for ge
 nome stability and regulation of gene expression. A deeper understanding o
 f how chromatin folds into higher-order domains to create a functional lan
 dscape for transcription remained elusive due to the lack of appropriate h
 igh-resolution single-cell analysis methods. \nBy live and fixed cell supe
 r-resolution 3D structured illumination microscopy (3D-SIM) we have been a
 ble to resolve a dynamic 3D landscape\, consisting of a heterogeneous netw
 ork of 300-700-nm-wide chromatin domain clusters\, that are approximately 
 in the size scale of TADs confirmed by FISH. This network is co-aligned wi
 th a DNA-free interchromatin network of similar dimension leading to nucle
 ar pores. Applying a custom ‘deep content’ quantitative imaging workfl
 ow we systematically mapped the spatial distribution of a wide range of ep
 igenetic marker and structural proteins. We find transcriptionally active/
 permissive chromatin marks as well as cohesin and CTCF highly enriched at 
 decondensed domain surfaces exposed to interchromatin space\, whereas repr
 essive chromatin marks are located towards the interior of domains. This c
 orrelation between nano-scale chromatin conformation and epigenetic marks/
 states persists after ablation of cohesin function\, is enhanced upon biop
 hysical perturbation\, such as ATP depletion and induced chromatin hyper-c
 ondensation\, and temporarily lost in post-replicative chromatin.\nOur fin
 dings support a model of a higher-order chromatin architecture on the size
  level of TADs that creates distinct functional environments through the a
 ction of biophysical forces other than cohesin-CTCF mediated looping inter
 action\, that may contribute to regulate genome function through physical 
 accessibility.
LOCATION:Babraham - The Brian Heap Seminar Room
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