An effect of DNA sequence on nucleosome occupancy and removal.
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ABSTRACT:
SUBMITTER: Wang X
PROVIDER: S-EPMC3071895 | biostudies-literature | 2011 Apr
REPOSITORIES: biostudies-literature
Publications
An effect of DNA sequence on nucleosome occupancy and removal.
Wang Xin X Bryant Gene O GO Floer Monique M Spagna Dan D Ptashne Mark M
Nature structural & molecular biology 20110306 4
A barrier phases nucleosomes at the yeast (Saccharomyces cerevisiae) GAL1-GAL10 genes. Here we separate nucleosome positioning from occupancy and show that the degree of occupancy of these phased sites is predictably determined by the underlying DNA sequences. As this occupancy is increased (by sequence alteration), nucleosome removal upon induction is decreased, as is mRNA production. These results explain why promoter sequences have evolved to form nucleosomes relatively inefficiently. ...[more]
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Project description:The human transcription factor TP53 is a pivotal roadblock against cancer. A key unresolved question is how the p53 protein selects its genomic binding sites in vivo out of a large pool of potential consensus sites. We hypothesized that chromatin may play a significant role in this site-selection process. To test this, we used a custom DNA microarray to measure p53 binding at approximately 2000 sites predicted to possess high-sequence specificity, and identified both strongly bound and weakly bound sites. When placed within a plasmid, weakly bound sites become p53 responsive and regain p53 binding when stably integrated into random genomic locations. Notably, strongly bound sites reside preferentially within genomic regions whose DNA sequence is predicted to encode relatively high intrinsic nucleosome occupancy. Using in vivo nucleosome occupancy measurements under conditions where p53 is inactive, we experimentally confirmed this prediction. Furthermore, upon p53 activation, nucleosomes are partially displaced from a relatively broad region surrounding the bound p53 sites, and this displacement is rapidly reversed upon inactivation of p53. Thus, in contrast to the general assumption that transcription-factor binding is preferred in sites that have low nucleosome occupancy prior to factor activation, we find that p53 binding occurs preferentially within a chromatin context of high intrinsic nucleosome occupancy.
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Project description:BackgroundSignificant differences in G+C content between different isochore types suggest that the nucleosome positioning patterns in DNA of the isochores should be different as well.ResultsExtraction of the patterns from the isochore DNA sequences by Shannon N-gram extension reveals that while the general motif YRRRRRYYYYYR is characteristic for all isochore types, the dominant positioning patterns of the isochores vary between TAAAAATTTTTA and CGGGGGCCCCCG due to the large differences in G+C composition. This is observed in human, mouse and chicken isochores, demonstrating that the variations of the positioning patterns are largely G+C dependent rather than species-specific. The species-specificity of nucleosome positioning patterns is revealed by dinucleotide periodicity analyses in isochore sequences. While human sequences are showing CG periodicity, chicken isochores display AG (CT) periodicity. Mouse isochores show very weak CG periodicity only.ConclusionsNucleosome positioning pattern as revealed by Shannon N-gram extension is strongly dependent on G+C content and different in different isochores. Species-specificity of the pattern is subtle. It is reflected in the choice of preferentially periodical dinucleotides.
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