Variable Nucleosome Spacing Reveals Principles of Chromatin Organization (2012)

Undergraduates: Timothy Palpant, Colin Lickwar

Faculty Advisor: Jason Lieb
Department: Biology

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In eukaryotic cells, access to genetic information is dynamically regulated by proteins that complex with DNA, collectively called chromatin. The fundamental unit of chromatin is the nucleosome, and periodically spaced nucleosomes regulate nuclear processes including transcription, splicing, and DNA replication. The factors that establish nucleosome positions across the genome remain controversial. In the emerging statistical positioning model, nucleosomes become oriented in regular arrays around sequence-specific energetic boundaries. In order to quantitatively test the statistical positioning hypothesis in vivo, we produced genome-wide, base pair resolution maps of nucleosome positions in several strains of the budding yeast Saccharomyces cerevisiae by MNase-seq. In support of statistical positioning, we found that different strains exhibited different intragenic nucleosome spacing, while the location of boundaries remained relatively constant. We further found that inter-boundary distances were preferentially quantized in integer multiples of the nucleosome spacing, and that differences in nucleosome spacing disrupted the number of nucleosomes that fit between boundaries. These results suggest that nucleosome spacing is precisely regulated in order to establish gene-specific chromatin organization. This work suggests a general mechanism by which chromatin structure might be established and regulated without constraining the evolution of protein coding sequences.