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SUMMARY:Organisation and Regulation of DNA supercoiling domains in Mammali
 an Chromatin. - Professor Nick Gilbert\, MRC Human Genetics Unit\, The Uni
 versity of Edinburgh
DTSTART:20141023T133000Z
DTEND:20141023T143000Z
UID:TALK54022@talks.cam.ac.uk
CONTACT:Caroline Newnham
DESCRIPTION:Chromatin is folded at different levels of organisation from t
 he fundamental nucleosomal fibre to large-scale chromatin structures. We h
 ave recently developed a method for analysing patterns of supercoiling and
  have shown that the human genome is organised into large supercoiling dom
 ains that are regulated by transcription and topoisomerase activity. To ex
 tend this work we have now investigated DNA supercoiling around transcript
 ion start sites in human cells at high resolution and reveal that CpG isla
 nd and non-CpG island genes have different patterns of DNA structure. Our 
 data indicates that one role of CpG islands is to stabilise DNA structure 
 and act as a buffer to resist the topological alterations caused by excess
  DNA supercoiling which could otherwise impact on transcription factor bin
 ding. Previously we argued that DNA supercoiling and transcription could i
 nfluence large scale chromatin structure however the molecular mechanisms 
 linking these processes remain poorly understood. SAF-A (scaffold attachme
 nt factor A) was identified as a nuclear scaffold component and encodes bo
 th DNA binding and RNA binding domains. By immunofluorescence we observed 
 that SAF-A is associated with many euchromatic loci but excluded from high
 ly condensed heterochromatin regions\, suggesting that it might be importa
 nt for regulating global chromatin structures. To better understand the ro
 le of SAF-A\, we analysed chromatin compaction using DNA-FISH and RNAi. De
 pletion of SAF-A caused significant compaction of both the X chromosome an
 d chromosome 11 territories. Further higher resolution analysis showed tha
 t gene-rich regions enriched in “open” chromatin were compacted\, but 
 gene-poor regions were unaffected. Consistently\, SAF-A binds to large dom
 ains around gene-rich regions but appears excluded from gene poor areas. P
 reviously we showed that gene-rich regions were decompacted by transcripti
 on\; we now show that SAF-A depletion also promotes the compaction of gene
 -rich regions indicating they may operate in the same pathway. We therefor
 e propose that SAF-A is recruited to gene-rich regions by RNA and facilita
 tes transcriptional regulation by maintaining an “open” chromatin stru
 cture\, possibly by modulating large scale chromatin topology. \n\n
LOCATION:Part II Room\, Department of Genetics
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