BEGIN:VCALENDAR
VERSION:2.0
PRODID:-//Talks.cam//talks.cam.ac.uk//
X-WR-CALNAME:Talks.cam
BEGIN:VEVENT
SUMMARY:Chromosomes as topological machines-the role of DNA thermodynamics
  - Travers\, A (University of Cambridge)
DTSTART:20120905T091000Z
DTEND:20120905T095000Z
UID:TALK39542@talks.cam.ac.uk
CONTACT:Mustapha Amrani
DESCRIPTION:The chirality of the DNA molecule underpins its ability to par
 tition superhelicity between twist and writhe. We argue that manipulation 
 of superhelical density and of partitioning by topological devices and pro
 cessive ATP-dependent motors (DNA and RNA polymerases and topoisomerases) 
 is a fundamental property of both bacterial and eukaryotic chromosomes. On
  this view chromosomes act as machines in which topological transitions op
 erate at several functional levels - local (e.g. transcription initiation 
 sites)\, regional (constrained superhelical domains) and global (chromosom
 es) levels. \n\nThe partition between twist and writhe is dependent in par
 t on the sequence of DNA. We have shown that in the E. coli chromosome gra
 dients of DNA gyrase binding sites from the origin to the terminus of DNA 
 replication along both replichores correlate with temporal patterns of gen
 e expression during the growth cycle such that genes expressed during expo
 nential growth are preferentially located in the Ori-proximal region. Thes
 e observations imply that during exponential growth there exist gradients 
 of superhelical density from the origin to the terminus. Intriguingly the 
 chromosomal DNA sequences exhibit\, on average\, a gradient of DNA stackin
 g energy in the same direction. We argue that this gradient in the physico
 chemical properties of DNA integrates the functional response to changes i
 n superhelical density and to regulation by abundant nucleoid-associated p
 roteins. \n\nWe further show that the genetic and chromatin organisation i
 n yeast chromatin assembled both in vitro and in vivo is highly dependent 
 on\, the stacking/melting energies of DNA sequences. The regions of chromo
 somes that are sites for topological manipulation (such as transcription a
 nd replication initiation sites and preferred sites for topoisomerase II) 
 correlate strongly with low stacking energies and high flexibility. Such r
 egions concomitantly exhibit low nucleosome occupancy. We conclude that th
 e most flexible DNA sequences are\, counter-intuitively\, poor substrates 
 for octamer deposition. In contrast high nucleosome occupancy correlates w
 ith DNA sequences of moderately high stacking energies. In such relatively
  stiff sequences positioned nucleosomes can often be related to a bending 
 anisotropy appropriate for nucleosome formation.\n\n
LOCATION:Seminar Room 1\, Newton Institute
END:VEVENT
END:VCALENDAR