ABSTRACT
Nucleosomes have structural and regulatory functions in all eukaryotic DNA-templated processes. The position of nucleosomes on DNA and the stability of the underlying histone-DNA interactions affect the access of regulatory proteins to DNA. Both stability and position are regulated through DNA sequence, histone post-translational modifications, histone variants, chromatin remodelers, and transcription factors. Here, we explored the functional implications of nucleosome properties on gene expression and development in C. elegans embryos. We performed a time-course of micrococcal nuclease (MNase) digestion, and measured the relative sensitivity or resistance of nucleosomes throughout the genome. Fragile nucleosomes were defined by nucleosomal DNA fragments recoverable preferentially in early MNase-digestion time points. We found fragile nucleosomes at locations where we expected to find destabilized nucleosomes, like transcription factor binding sites where nucleosomes compete with DNA-binding factors. Contrary to our expectation, the presence of fragile nucleosomes in gene promoters was anti-correlated with transcriptional activity. Instead, genes with fragile nucleosomes in their promoters tended to be expressed in a context-specific way, operating in neuronal response, the immune system, and stress response. Nucleosome fragility at these promoters was strongly and positively correlated with the AT content of the underlying DNA. There was not a strong correlation between promoter nucleosome fragility and the levels of histone modifications or histone variants. Our data suggest that in C. elegans promoters, nucleosome fragility is primarily a DNA-encoded feature that poises genes for future context-specific activation in response to environmental stress and developmental cues.
