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SUMMARY:Gene regulation in the context of variability in DNA sequence and 
 structure - Teresa Przytycka\, NCBI\, NLM\, National Institutes of Health
DTSTART:20100903T133000Z
DTEND:20100903T143000Z
UID:TALK26022@talks.cam.ac.uk
CONTACT:Dr Madan Babu Mohan
DESCRIPTION:New experimental techniques facilitating genome-wide measureme
 nts of various molecular quantities provide us with an unprecedented oppor
 tunity to gain new insights into functioning of cellular systems.  Perhaps
  most dramatic recent advances relate to gaining understanding of the comp
 lexity of gene regulation. In this talk\, I will discuss our outgoing rese
 arch on the impact of two types of genomic changes – (i) gene copy numbe
 r variations (CNV) and (ii) DNA secondary structure.\n\nGene duplication a
 nd deletions are common features of somatic cell mutations in cancer.  How
  the genotypic changes are propagated along molecular pathways? On one han
 d\, in complex diseases\, different genotypic perturbations often lead to 
 the same disease phenotype by dys-regulating common pathways. Discovering 
 such pathways is the focus on our computational study of brain cancer.  On
  the other hand\, our studies in fly (collaboration with experimental grou
 p of Brian Oliver\, NIDDK/NIH) suggest that the effect of gene copy number
  variations is often “buffered” through cellular feedback. Both studie
 s underscore of importance considering cellular network in studies of the 
 effect of CNV on gene expression.\n\nThe so called non-B-DNA structures\, 
 including G4\, Z-DNA\, SIDD\, have been long implied to play regulatory ro
 les. However capturing these structures in vivo on genome-wide scale has b
 een elusive.  We have been able to achieve this goal using deep sequencing
  technology (collaboration with groups of David Leven’s NCI/NIH and Rafa
 el Casellas\, NIAMS/NIH). We have compared\, for the first time on such sc
 ale\, the experimental data and to the genomic regions computationally pre
 dicted to have a high propensity to form non-B DNA conformations. We found
  that not only experimentally detected non-B DNA regions have a significan
 t overlap with computationally predicted regions\, but also various comput
 ationally classified non-B DNA conformations have different experimentally
  derived signatures. This study offers not only strong evidence for the in
  vivo formation of the alternative but also provides the first look at the
 ir genome-wide landscape and possible role in gene regulation.
LOCATION:Structural Studies Seminar Room\, MRC Laboratory of Molecular Bio
 logy\, Cambridge\, UK
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