long-range allosteric effect in gene transcriptional regulation

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long-range allosteric effect in gene
transcriptional regulation
International Symposium on the Recent Progress in
Quantitative and Systems Biology , Dec 9-11, The
Chinese University of Hong Kong

• Ming Li
• Graduate School, CAS
• Zhong-can Ou-yang
• Institute of Theoretical Physics, CAS

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Outline

• Stressed state of DNA in vivo
• Model of topologically constrained DNA
• and duplex separation
• Long-range Allosteric Effect and Database
  investigation a case study

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Part IStressed state of DNA in vivo
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4 types of nucleotides Adenine,
Thymine Guanine, Cytosine Waston-Crick base
pair A-T, G-C Intrinsic right-handed helix,
stiff polymer B-DNA uniform,
sequence-independent
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DNA Mechanics Plays a Role ?

• DNA centimeters
• Nucleus microns
• compaction ratio 1/8000
• Twisting dsDNA is a highly efficient way for
  compaction !
• Is the elastic response vital for DNA functioning
  ?

eukaryote
prokaryote
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Chromosome Assembly Chromatin Loop Model

• Hierarchical architecture
• DNA Stressed
• S/MARs
• Boundaries of topologically-independent domains ?

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Genomic DNA is potentially under unwinding stress

• DNA segment per nucleosome 167 bp
• The segment is actually undertwisted
• one helical turn unwound per nucleosome.
• torsional stress generated

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Sequence Heterogeneity ? Structure
Heterogeneity
Unstacking
Chirality Variable
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Unwinding can promote local strand-separation
(bubble) as well as global axis-supercoiling
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In summary
Unwinding stress in vivo Plays the Key Role in
Bubble formation !
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Part IIBenham Model of topologically
constrained DNA sequence-dependent duplex
separation
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Characterizing the degree of unwinding