A genomic code for nucleosome positioning

Eran Segal; Yvonne Fondufe-Mittendorf; Lingyi Chen; Annchristine Thåström; Yair Field; Irene K. Moore; Ji Ping Z. Wang; Jonathan Widom

doi:10.1038/nature04979

A genomic code for nucleosome positioning

Eran Segal, Yvonne Fondufe-Mittendorf, Lingyi Chen, Annchristine Thåström, Yair Field, Irene K. Moore, Ji Ping Z. Wang, Jonathan Widom

Molecular and Cellular Biochemistry

Research output: Contribution to journal › Article › peer-review

1241 Scopus citations

Abstract

Eukaryotic genomes are packaged into nucleosome particles that occlude the DNA from interacting with most DNA binding proteins. Nucleosomes have higher affinity for particular DNA sequences, reflecting the ability of the sequence to bend sharply, as required by the nucleosome structure. However, it is not known whether these sequence preferences have a significant influence on nucleosome position in vivo, and thus regulate the access of other proteins to DNA. Here we isolated nucleosome-bound sequences at high resolution from yeast and used these sequences in a new computational approach to construct and validate experimentally a nucleosome-DNA interaction model, and to predict the genome-wide organization of nucleosomes. Our results demonstrate that genomes encode an intrinsic nucleosome organization and that this intrinsic organization can explain ∼50% of the in vivo nucleosome positions. This nucleosome positioning code may facilitate specific chromosome functions including transcription factor binding, transcription initiation, and even remodelling of the nucleosomes themselves.

Original language	English
Pages (from-to)	772-778
Number of pages	7
Journal	Nature
Volume	442
Issue number	7104
DOIs	https://doi.org/10.1038/nature04979
State	Published - Aug 17 2006

Bibliographical note

Funding Information:
Acknowledgements We thank A. Travers for providing the chicken nucleosome core DNA sequences; M. Kubista for providing selected mouse DNA sequences; O. Rando for providing access to their nucleosome data before publication; J. Lieb, E. Nili and P. Jones for sharing their respective unpublished data; Y. Lubling for creating the supplementary website; and H. Chang, N. Friedman, U. Gaul, A. Matouschek, B. Meyer, M. Ptashne, E. Siggia and A. Tanay for useful comments on the manuscript. E.S. was supported by a fellowship from the Center for Studies in Physics and Biology at Rockefeller University and by an NIH grant. J.W. thanks the Center for their hospitality during a sabbatical. J.-P.Z.W. acknowledges support from an NIH grant and J.W. acknowledges support from two NIH grants. E.S. is the incumbent of the Soretta and Henry Shapiro career development chair.

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title = "A genomic code for nucleosome positioning",

abstract = "Eukaryotic genomes are packaged into nucleosome particles that occlude the DNA from interacting with most DNA binding proteins. Nucleosomes have higher affinity for particular DNA sequences, reflecting the ability of the sequence to bend sharply, as required by the nucleosome structure. However, it is not known whether these sequence preferences have a significant influence on nucleosome position in vivo, and thus regulate the access of other proteins to DNA. Here we isolated nucleosome-bound sequences at high resolution from yeast and used these sequences in a new computational approach to construct and validate experimentally a nucleosome-DNA interaction model, and to predict the genome-wide organization of nucleosomes. Our results demonstrate that genomes encode an intrinsic nucleosome organization and that this intrinsic organization can explain ∼50% of the in vivo nucleosome positions. This nucleosome positioning code may facilitate specific chromosome functions including transcription factor binding, transcription initiation, and even remodelling of the nucleosomes themselves.",

author = "Eran Segal and Yvonne Fondufe-Mittendorf and Lingyi Chen and Annchristine Th{\aa}str{\"o}m and Yair Field and Moore, {Irene K.} and Wang, {Ji Ping Z.} and Jonathan Widom",

note = "Funding Information: Acknowledgements We thank A. Travers for providing the chicken nucleosome core DNA sequences; M. Kubista for providing selected mouse DNA sequences; O. Rando for providing access to their nucleosome data before publication; J. Lieb, E. Nili and P. Jones for sharing their respective unpublished data; Y. Lubling for creating the supplementary website; and H. Chang, N. Friedman, U. Gaul, A. Matouschek, B. Meyer, M. Ptashne, E. Siggia and A. Tanay for useful comments on the manuscript. E.S. was supported by a fellowship from the Center for Studies in Physics and Biology at Rockefeller University and by an NIH grant. J.W. thanks the Center for their hospitality during a sabbatical. J.-P.Z.W. acknowledges support from an NIH grant and J.W. acknowledges support from two NIH grants. E.S. is the incumbent of the Soretta and Henry Shapiro career development chair.",

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AU - Widom, Jonathan

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AB - Eukaryotic genomes are packaged into nucleosome particles that occlude the DNA from interacting with most DNA binding proteins. Nucleosomes have higher affinity for particular DNA sequences, reflecting the ability of the sequence to bend sharply, as required by the nucleosome structure. However, it is not known whether these sequence preferences have a significant influence on nucleosome position in vivo, and thus regulate the access of other proteins to DNA. Here we isolated nucleosome-bound sequences at high resolution from yeast and used these sequences in a new computational approach to construct and validate experimentally a nucleosome-DNA interaction model, and to predict the genome-wide organization of nucleosomes. Our results demonstrate that genomes encode an intrinsic nucleosome organization and that this intrinsic organization can explain ∼50% of the in vivo nucleosome positions. This nucleosome positioning code may facilitate specific chromosome functions including transcription factor binding, transcription initiation, and even remodelling of the nucleosomes themselves.

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A genomic code for nucleosome positioning

Abstract

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