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A Genomic Code for Nucleosome Positioning

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

Eukaryotic genomes are packaged into nucleosome particles, which occlude their DNA from interaction with most DNA binding proteins. Nucleosomes have higher affinity for particular DNA sequences, reflecting the sequences' ability to sharply bend, as required by the nucleosome structure. However, whether these sequence preferences have a significant influence on nucleosome positions in vivo, and thus regulate the access of other proteins to DNA is not known. Here, we isolated nucleosome-bound sequences at high resolution from yeast, and used these sequences in a novel computational approach to construct and experimentally validate 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 itself can explain ~50% of the in vivo nucleosome positions. This nucleosome positioning code facilitates many specific chromosome functions, including transcription factor binding, transcription initiation, and even remodeling of the nucleosomes themselves.

Illustration of key periodic dinucleotide features
in our predicted nucleosome-DNA interaction model