The DNA-encoded nucleosome organization of a eukaryotic genome

By Noam Kaplan, Irene K. Moore, Yvonne Fondufe-Mittendorf, A. Gossett, Desiree Tillo, Yair Field, E. Leproust, Timothy R. Hughes, J. Lieb, Jonathan Widom and 1 more. Nature, 2008

1,273 citations recorded by the source corpus.

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 ∼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.

Subfields: Molecular Biology, Plant Science

View Paper: https://www.semanticscholar.org/paper/d83d1ee9d0aab5966572e55d5d122d7181c29eaa

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Citations in the corpus

Chromatin organization marks exon-intron structure (2009, background): “DNA sequence modulates how and where the DNA is packaged around nucleosomes, a concept embodied in the idea of a 'chromatin code': this information is to a great extent encoded directly within the genome sequenc”
Recombination centres and the orchestration of V(D)J recombination (2011, background): “This is consistent with the emerging view that although the primary DNA sequence directly influences nucleosome positioning, many other factors (such as remodelling complexes, bound proteins, promoter-loaded RNA polymerase II and DNA methylation) also have important role”
Making the Bend: DNA Tertiary Structure and Protein-DNA Interactions (2014, background): “In yeast, runs of about 20 bp of such poly-TA sequences are found upstream from promoter elements of constitutively active transcribed genes [45,46].”
Transcription factor binding in human cells occurs in dense clusters formed around cohesin anchor sites. (2013, positive): “A model of nucleosome DNA-binding preferences (Kaplan et al., 2009) could not explain the decrease in nucleosome occupancy at the cohesin position, even though it correctly predicted an increased occupancy flanking the cohesin sites.”
Structure and mechanism of the chromatin remodelling factor ISW1a (2011, background): “This result confirms three expectations from our model: (1) ISW1a would be oriented on this dinucleosome substrate, most probably through Ioc3 CLB interaction with the 29-bp extension; (2) the I/E-nucleosome would be static; and (3) the I-nucleosome would be mobile through association with the Isw1 ”
Organization of Chromatin by Intrinsic and Regulated Phase Separation (2019, background): “DNA sequences phased in TA:AT:TT:AA dinucleotide base pairs position nucleosomes in vitro and in vivo (Kaplan et al., 2009; Lowary and Widom, 1998; Struhl and Segal, 2013).”
H2A.Z-containing nucleosomes mediate the thermosensory response in Arabidopsis. (2010, positive): “Values are mean ± SD from one representative experiment. arising from RNA Pol II-mediated displacement of nucleosomes, as well as being predicted to have a well-ordered nucleosome structure using a recent model (Kaplan et al., 2009).”