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Predicting Human Nucleosome Occupancy from Primary Sequence

Nucleosomes are the fundamental repeating unit of chromatin and comprise the structural building blocks of the living eukaryotic genome. Micrococcal nuclease (MNase) has long been used to delineate nucleosomal organization. Microarray-based nucleosome mapping experiments in yeast chromatin have reve...

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Autores principales: Gupta, Shobhit, Dennis, Jonathan, Thurman, Robert E., Kingston, Robert, Stamatoyannopoulos, John A., Noble, William Stafford
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2515632/
https://www.ncbi.nlm.nih.gov/pubmed/18725940
http://dx.doi.org/10.1371/journal.pcbi.1000134
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author Gupta, Shobhit
Dennis, Jonathan
Thurman, Robert E.
Kingston, Robert
Stamatoyannopoulos, John A.
Noble, William Stafford
author_facet Gupta, Shobhit
Dennis, Jonathan
Thurman, Robert E.
Kingston, Robert
Stamatoyannopoulos, John A.
Noble, William Stafford
author_sort Gupta, Shobhit
collection PubMed
description Nucleosomes are the fundamental repeating unit of chromatin and comprise the structural building blocks of the living eukaryotic genome. Micrococcal nuclease (MNase) has long been used to delineate nucleosomal organization. Microarray-based nucleosome mapping experiments in yeast chromatin have revealed regularly-spaced translational phasing of nucleosomes. These data have been used to train computational models of sequence-directed nuclesosome positioning, which have identified ubiquitous strong intrinsic nucleosome positioning signals. Here, we successfully apply this approach to nucleosome positioning experiments from human chromatin. The predictions made by the human-trained and yeast-trained models are strongly correlated, suggesting a shared mechanism for sequence-based determination of nucleosome occupancy. In addition, we observed striking complementarity between classifiers trained on experimental data from weakly versus heavily digested MNase samples. In the former case, the resulting model accurately identifies nucleosome-forming sequences; in the latter, the classifier excels at identifying nucleosome-free regions. Using this model we are able to identify several characteristics of nucleosome-forming and nucleosome-disfavoring sequences. First, by combining results from each classifier applied de novo across the human ENCODE regions, the classifier reveals distinct sequence composition and periodicity features of nucleosome-forming and nucleosome-disfavoring sequences. Short runs of dinucleotide repeat appear as a hallmark of nucleosome-disfavoring sequences, while nucleosome-forming sequences contain short periodic runs of GC base pairs. Second, we show that nucleosome phasing is most frequently predicted flanking nucleosome-free regions. The results suggest that the major mechanism of nucleosome positioning in vivo is boundary-event-driven and affirm the classical statistical positioning theory of nucleosome organization.
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spelling pubmed-25156322008-08-22 Predicting Human Nucleosome Occupancy from Primary Sequence Gupta, Shobhit Dennis, Jonathan Thurman, Robert E. Kingston, Robert Stamatoyannopoulos, John A. Noble, William Stafford PLoS Comput Biol Research Article Nucleosomes are the fundamental repeating unit of chromatin and comprise the structural building blocks of the living eukaryotic genome. Micrococcal nuclease (MNase) has long been used to delineate nucleosomal organization. Microarray-based nucleosome mapping experiments in yeast chromatin have revealed regularly-spaced translational phasing of nucleosomes. These data have been used to train computational models of sequence-directed nuclesosome positioning, which have identified ubiquitous strong intrinsic nucleosome positioning signals. Here, we successfully apply this approach to nucleosome positioning experiments from human chromatin. The predictions made by the human-trained and yeast-trained models are strongly correlated, suggesting a shared mechanism for sequence-based determination of nucleosome occupancy. In addition, we observed striking complementarity between classifiers trained on experimental data from weakly versus heavily digested MNase samples. In the former case, the resulting model accurately identifies nucleosome-forming sequences; in the latter, the classifier excels at identifying nucleosome-free regions. Using this model we are able to identify several characteristics of nucleosome-forming and nucleosome-disfavoring sequences. First, by combining results from each classifier applied de novo across the human ENCODE regions, the classifier reveals distinct sequence composition and periodicity features of nucleosome-forming and nucleosome-disfavoring sequences. Short runs of dinucleotide repeat appear as a hallmark of nucleosome-disfavoring sequences, while nucleosome-forming sequences contain short periodic runs of GC base pairs. Second, we show that nucleosome phasing is most frequently predicted flanking nucleosome-free regions. The results suggest that the major mechanism of nucleosome positioning in vivo is boundary-event-driven and affirm the classical statistical positioning theory of nucleosome organization. Public Library of Science 2008-08-22 /pmc/articles/PMC2515632/ /pubmed/18725940 http://dx.doi.org/10.1371/journal.pcbi.1000134 Text en Gupta et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Gupta, Shobhit
Dennis, Jonathan
Thurman, Robert E.
Kingston, Robert
Stamatoyannopoulos, John A.
Noble, William Stafford
Predicting Human Nucleosome Occupancy from Primary Sequence
title Predicting Human Nucleosome Occupancy from Primary Sequence
title_full Predicting Human Nucleosome Occupancy from Primary Sequence
title_fullStr Predicting Human Nucleosome Occupancy from Primary Sequence
title_full_unstemmed Predicting Human Nucleosome Occupancy from Primary Sequence
title_short Predicting Human Nucleosome Occupancy from Primary Sequence
title_sort predicting human nucleosome occupancy from primary sequence
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2515632/
https://www.ncbi.nlm.nih.gov/pubmed/18725940
http://dx.doi.org/10.1371/journal.pcbi.1000134
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