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SUMMARY:Modeling chromatin fibre folding for human embryonic stem cells an
 d cancer cells - Maggioni\, F (University of Bergamo\, Italy)
DTSTART:20120903T144000Z
DTEND:20120903T150000Z
UID:TALK39500@talks.cam.ac.uk
CONTACT:Mustapha Amrani
DESCRIPTION:All diverse cell types in an organism essentially have an iden
 tical genome. Generation of\ntissue specific cells is through an epigenomi
 c process in which progressive alterations in\nthe chromatin state generat
 es lineage committed cells from pluripotent embryonic stem\ncells. Ultimat
 ely\, establishment of terminally differentiated cells results in a stable
 \nchromatin state.\nChromatin modification can be studied by chromatin imm
 unoprecipitation (ChIP) that\nidentifies regions that are over-represented
  as transcriptionally active sequences.\nIn this talk we describe chromati
 n-state maps for pluripotent\, cancer and lineagecommitted\ncells using th
 ree-dimensional modelling of fibre conformation. The model\ntakes into acc
 ount of the local structure of chromatin organised into euchromatin (open\
 nchromatin)\, permissive for gene activation\, and heterochromatin (closed
  chromatin)\,\ntranscriptionally silenced. Open chromatin is assumed to be
  modelled by a linker DNA\nwhile the closed chromatin by means of a soleno
 id structure in which DNA winds onto\nsix nucleosome spools per turn with 
 two left-handed superhelical turns around an histone\noctamer. The model r
 epresents a single gyre of a solenoid by means of a torus knot that\nwinds
  around a torus once in the longitudinal direction and twelve in the merid
 ian\ndirection. Closed and open chromatin is then connected by means of pi
 ecewise\npolynomial transformations based on cubic Hermite spline function
 s. As reprogramming\nprocess is associated both with pluripotency and the 
 neoplastic process\, our analyses\npotentially identify cancer-related epi
 genetic abnormalities. Chromatin fibre\nconformation are compared in terms
  of geometric quantities such as curvature and\ntorsion localization\, and
  relative rates\, in relation to filament compaction and packing\nefficien
 cy. This study provides information on relationships between geometry and 
 the\ntranscriptional regulation in stem cells and cancer cells contributin
 g to pluripotency and\nself-renewal.\n
LOCATION:Seminar Room 1\, Newton Institute
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