Global remodeling of nucleosome positions in C.elegans
In vitro nucleosomes formed on C. elegans DNA cut by restriction enzymes
Chromatin architecture in metazoan genomes is affected by intrinsic histone-DNA sequence preferences, steric exclusion between nucleosome particles, formation of higher-order structures, and in vivo activity of chromatin remodeling enzymes and other DNA-associated factors. To disentangle sequence-dependent nucleosome positioning from other effects, we have created two high-throughput maps of nucleosomes assembled in vitro on genomic DNA from the nematode worm Caenorhabditis elegans. A comparison of in vitro nucleosome positions with those observed in a mixed-stage, mixed-tissue population of C. elegans cells reveals that intrinsic sequence preferences are overwritten on the genomic scale. Indeed, sequence-specific models predict that G/C dinucleotides are the most favorable for nucleosome formation in vitro but not in vivo. Furthermore, the majority of well-positioned in vivo nucleosomes do not occupy thermodynamically favorable sequences observed in vitro. In vivo, nucleosome sequence read coverage is lower in chromosomal arms relative to central regions and is thus broadly anticorrelated with the occupancy profile of the trans33membrane protein LEM-2 which mediates chromosome attachment to the nuclear envelope. Finally, we find that exons are intrinsically more amenable to nucleosome formation compared to introns. Nucleosome occupancy of introns and exons consistently increases with G/C content in vitro but not in vivo, in agreement with our observation that enrichment of G/C dinucleotides does not strongly promote in vivo nucleosome formation. Overall, our findings underscore the complexity of chromatin architecture in higher eukaryotes and the sometimes antagonistic roles of intrinsic sequence preferences and active nucleosome repositioning in directing gene transcription and other vital chromatin functions.