Mapping nucleosome positions using DNase-seq
- Jianling Zhong,
- Kaixuan Luo,
- Peter S Winter,
- Gregory E Crawford,
- Edwin S Iversen and
- Alexander J. Hartemink1
- ↵* Corresponding author; email: amink{at}cs.duke.edu
Abstract
As the fundamental units of chromatin, nucleosomes contribute to virtually all aspects of genome function. Common methods for mapping nucleosome positions rely on genome cleavage using micrococcal nuclease (MNase), or more recently, genetically-modified histones. Though deoxyribonuclease I (DNase I) was used to probe the structure of nucleosomes in the 1960s and 70s, in the current high-throughput sequencing era, it has mainly been used to study genomic regions devoid of nucleosomes. Here, we reveal for the first time that DNase~I can be used to precisely map the (translational) positions of in vivo nucleosomes genome-wide. Specifically, exploiting a distinctive DNase~I cleavage profile within nucleosome-associated DNA---including a signature 10.3~bp oscillation that corresponds to accessibility of the minor groove as DNA winds around the nucleosome---we develop a Bayes-factor--based method that can be used to map nucleosome positions along the genome. Compared to methods that require genetically-modified histones, our DNase-based approach is easily applied in any organism, which we demonstrate by producing maps in yeast and human. Compared to MNase-based methods that map nucleosomes based on cuts in linker regions, we utilize DNase I cuts both within and outside nucleosomal DNA and the oscillatory nature of the DNase I cleavage profile within nucleosomal DNA enables us to identify translational positioning details not apparent in MNase digestion of linker DNA. Because the oscillatory pattern corresponds to nucleosome rotational positioning, it also reveals the rotational context of transcription factor (TF) binding sites. We show that potential binding sites within nucleosome-associated DNA are often centered preferentially on an exposed major or minor groove. This preferential localization may modulate TF interaction with nucleosome-associated DNA as TFs search for binding sites.
- Received June 9, 2015.
- Accepted January 14, 2016.
- Published by Cold Spring Harbor Laboratory Press
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