Quantitative test of the barrier nucleosome model for statistical positioning of nucleosomes up- and downstream of transcription start sites
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vor 13 Jahren
The positions of nucleosomes in eukaryotic genomes determine which
parts of the DNA sequence are readily accessible for regulatory
proteins and which are not. Genome-wide maps of nucleosome
positions have revealed a salient pattern around transcription
start sites, involving a nucleosome-free region (NFR) flanked by a
pronounced periodic pattern in the average nucleosome density.
While the periodic pattern clearly reflects well-positioned
nucleosomes, the positioning mechanism is less clear. A recent
experimental study by Mavrich et al. argued that the pattern
observed in Saccharomyces cerevisiae is qualitatively consistent
with a "barrier nucleosome model," in which the oscillatory pattern
is created by the statistical positioning mechanism of Kornberg and
Stryer. On the other hand, there is clear evidence for intrinsic
sequence preferences of nucleosomes, and it is unclear to what
extent these sequence preferences affect the observed pattern. To
test the barrier nucleosome model, we quantitatively analyze yeast
nucleosome positioning data both up- and downstream from NFRs. Our
analysis is based on the Tonks model of statistical physics which
quantifies the interplay between the excluded-volume interaction of
nucleosomes and their positional entropy. We find that although the
typical patterns on the two sides of the NFR are different, they
are both quantitatively described by the same physical model with
the same parameters, but different boundary conditions. The
inferred boundary conditions suggest that the first nucleosome
downstream from the NFR (the +1 nucleosome) is typically directly
positioned while the first nucleosome upstream is statistically
positioned via a nucleosome-repelling DNA region. These boundary
conditions, which can be locally encoded into the genome sequence,
significantly shape the statistical distribution of nucleosomes
over a range of up to approximately 1,000 bp to each side.
parts of the DNA sequence are readily accessible for regulatory
proteins and which are not. Genome-wide maps of nucleosome
positions have revealed a salient pattern around transcription
start sites, involving a nucleosome-free region (NFR) flanked by a
pronounced periodic pattern in the average nucleosome density.
While the periodic pattern clearly reflects well-positioned
nucleosomes, the positioning mechanism is less clear. A recent
experimental study by Mavrich et al. argued that the pattern
observed in Saccharomyces cerevisiae is qualitatively consistent
with a "barrier nucleosome model," in which the oscillatory pattern
is created by the statistical positioning mechanism of Kornberg and
Stryer. On the other hand, there is clear evidence for intrinsic
sequence preferences of nucleosomes, and it is unclear to what
extent these sequence preferences affect the observed pattern. To
test the barrier nucleosome model, we quantitatively analyze yeast
nucleosome positioning data both up- and downstream from NFRs. Our
analysis is based on the Tonks model of statistical physics which
quantifies the interplay between the excluded-volume interaction of
nucleosomes and their positional entropy. We find that although the
typical patterns on the two sides of the NFR are different, they
are both quantitatively described by the same physical model with
the same parameters, but different boundary conditions. The
inferred boundary conditions suggest that the first nucleosome
downstream from the NFR (the +1 nucleosome) is typically directly
positioned while the first nucleosome upstream is statistically
positioned via a nucleosome-repelling DNA region. These boundary
conditions, which can be locally encoded into the genome sequence,
significantly shape the statistical distribution of nucleosomes
over a range of up to approximately 1,000 bp to each side.
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