A computational approach to map nucleosome positions and alternative chromatin states with base pair resolution.
Understanding chromatin function requires knowing the precise location of nucleosomes. MNase-seq methods have been widely applied to characterize nucleosome organization in vivo, but generally lack the accuracy to determine the precise nucleosome positions. Here we develop a computational approach leveraging digestion variability to determine nucleosome positions at a base-pair resolution from MNase-seq data. We generate a variability template as a simple error model for how MNase digestion affects the mapping of individual nucleosomes. Applied to both yeast and human cells, this analysis reveals that alternatively positioned nucleosomes are prevalent and create significant heterogeneity in a cell population. We show that the periodic occurrences of dinucleotide sequences relative to nucleosome dyads can be directly determined from genome-wide nucleosome positions from MNase-seq. Alternatively positioned nucleosomes near transcription start sites likely represent different states of promoter nucleosomes during transcription initiation. Our method can be applied to map nucleosome positions in diverse organisms at base-pair resolution.
Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States.|Faculty of Arts and Sciences Center for Systems Biology, Harvard University, Cambridge, USA.|Howard Hughes Medical Institute, Harvard University, Cambridge, United States.
Xu
0000-0002-1692-6823
X
Zhou
Department of Statistics, Harvard University, Cambridge, United States.
Alexander W
AW
Blocker
Department of Statistics, Harvard University, Cambridge, United States.|The Broad Institute of MIT and Harvard, Cambridge, United States.
Edoardo M
EM
Airoldi
Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States.|Faculty of Arts and Sciences Center for Systems Biology, Harvard University, Cambridge, USA.|Howard Hughes Medical Institute, Harvard University, Cambridge, United States.|Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States.
Erin K
0000-0002-2649-1018
EK
O'Shea
D002843:Chromatin; D019295:Computational Biology / Q000379:methods*; D004247:DNA / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D009707:Nucleosomes; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D017422:Sequence Analysis, DNA
D002843:Chromatin; D009707:Nucleosomes; D004247:DNA
MNase-seq; S. cerevisiae; base-pair resolution; computational biology; evolutionary biology; gene regulation; genomics; heterogenity; human; nucleosome position; systems biology; template-based model