The DNA-encoded nucleosome organization of a eukaryotic genome.
Nucleosome organization is critical for gene regulation. In living cells this organization is determined by multiple factors, including the action of chromatin remodellers, competition with site-specific DNA-binding proteins, and the DNA sequence preferences of the nucleosomes themselves. However, it has been difficult to estimate the relative importance of each of these mechanisms in vivo, because in vivo nucleosome maps reflect the combined action of all influencing factors. Here we determine the importance of nucleosome DNA sequence preferences experimentally by measuring the genome-wide occupancy of nucleosomes assembled on purified yeast genomic DNA. The resulting map, in which nucleosome occupancy is governed only by the intrinsic sequence preferences of nucleosomes, is similar to in vivo nucleosome maps generated in three different growth conditions. In vitro, nucleosome depletion is evident at many transcription factor binding sites and around gene start and end sites, indicating that nucleosome depletion at these sites in vivo is partly encoded in the genome. We confirm these results with a micrococcal nuclease-independent experiment that measures the relative affinity of nucleosomes for approximately 40,000 double-stranded 150-base-pair oligonucleotides. Using our in vitro data, we devise a computational model of nucleosome sequence preferences that is significantly correlated with in vivo nucleosome occupancy in Caenorhabditis elegans. Our results indicate that the intrinsic DNA sequence preferences of nucleosomes have a central role in determining the organization of nucleosomes in vivo.
Kaplan
Noam
N
Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel.
Moore
Irene K
IK
Fondufe-Mittendorf
Yvonne
Y
Gossett
Andrea J
AJ
Tillo
Desiree
D
Field
Yair
Y
LeProust
Emily M
EM
Hughes
Timothy R
TR
Lieb
Jason D
JD
Widom
Jonathan
J
Segal
Eran
E
D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics; D002645:Chickens; D019295:Computational Biology; D003198:Computer Simulation; D005057:Eukaryotic Cells / Q000378:metabolism*; D016681:Genome, Fungal / Q000235:genetics*; D008836:Micrococcal Nuclease / Q000378:metabolism; D009707:Nucleosomes / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000378:metabolism
D009707:Nucleosomes; D012333:RNA, Messenger; D014157:Transcription Factors; D008836:Micrococcal Nuclease