1. Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel
2. Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, 2153 Sheridan Road, Evanston, Illinois 60208, USA
3. Department of Statistics, Northwestern University, 2006 Sheridan Road, Evanston, Illinois 60208, USA

Correspondence to: Eran Segal¹Jonathan Widom² Correspondence and requests for materials should be addressed to E.S. (Email: eran.segal@weizmann.ac.il) or J.W. (Email: j-widom@northwestern.edu).

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.

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