DNase-seq predicts regions of rotational nucleosome stability across diverse human cell types

Deborah R. Winter, Lingyun Song, Sayan Mukherjee, Terrence S. Furey*, Gregory E. Crawford

*Corresponding author for this work

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

DNase-seq is primarily used to identify nucleosome-depleted DNase I hypersensitive (DHS) sites genome-wide that correspond to active regulatory elements. However, ∼40 yr ago it was demonstrated that DNase I also digests with a ∼10-bp periodicity around nucleosomes matching the exposure of the DNA minor groove as it wraps around histones. Here, we use DNase-seq data from 49 samples representing diverse cell types to reveal this digestion pattern at individual loci and predict genomic locations where nucleosome rotational positioning, the orientation of DNA with respect to the histone surface, is stably maintained. We call these regions DNase I annotated regions of nucleosome stability (DARNS). Compared to MNase-seq experiments, we show DARNS correspond well to annotated nucleosomes. Interestingly, many DARNS are positioned over only one side of annotated nucleosomes, suggesting that the periodic digestion pattern attenuates over the nucleosome dyad. DARNS reproduce the arrangement of nucleosomes around transcription start sites and are depleted at ubiquitous DHS sites. We also generated DARNS from multiple lymphoblast cell line (LCL) samples. We found that LCL DARNS were enriched at DHS sites present in most of the original 49 samples but absent in LCLs, while multi-cell-type DARNS were enriched at LCL-specific DHS sites. This indicates that variably open DHS sites are often occupied by rotationally stable nucleosomes in cell types where the DHS site is closed. DARNS provide additional information about precise DNA orientation within individual nucleosomes not available from other nucleosome positioning assays and contribute to understanding the role of chromatin in gene regulation.

Original languageEnglish (US)
Pages (from-to)1118-1129
Number of pages12
JournalGenome Research
Volume23
Issue number7
DOIs
StatePublished - Jul 1 2013

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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