Nucleosome Presence at AML-1 Binding Sites Inversely Correlates with Ly49 Expression: Revelations from an Informatics Analysis of Nucleosomes and Immune Cell Transcription Factors

PLoS Comput Biol. 2016 Apr 28;12(4):e1004894. doi: 10.1371/journal.pcbi.1004894. eCollection 2016 Apr.


Beyond its role in genomic organization and compaction, the nucleosome is believed to participate in the regulation of gene transcription. Here, we report a computational method to evaluate the nucleosome sensitivity for a transcription factor over a given stretch of the genome. Sensitive factors are predicted to be those with binding sites preferentially contained within nucleosome boundaries and lacking 10 bp periodicity. Based on these criteria, the Acute Myeloid Leukemia-1a (AML-1a) transcription factor, a regulator of immune gene expression, was identified as potentially sensitive to nucleosomal regulation within the mouse Ly49 gene family. This result was confirmed in RMA, a cell line with natural expression of Ly49, using MNase-Seq to generate a nucleosome map of chromosome 6, where the Ly49 gene family is located. Analysis of this map revealed a specific depletion of nucleosomes at AML-1a binding sites in the expressed Ly49A when compared to the other, silent Ly49 genes. Our data suggest that nucleosome-based regulation contributes to the expression of Ly49 genes, and we propose that this method of predicting nucleosome sensitivity could aid in dissecting the regulatory role of nucleosomes in general.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites / genetics
  • Cell Line
  • Chromosome Mapping
  • Computational Biology
  • Core Binding Factor Alpha 2 Subunit / genetics
  • Core Binding Factor Alpha 2 Subunit / metabolism*
  • Gene Expression Regulation
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Mice
  • Multigene Family
  • NK Cell Lectin-Like Receptor Subfamily A / genetics*
  • Nucleosomes / genetics*
  • Nucleosomes / immunology
  • Nucleosomes / metabolism*
  • Promoter Regions, Genetic
  • Protein Binding
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Core Binding Factor Alpha 2 Subunit
  • NK Cell Lectin-Like Receptor Subfamily A
  • Nucleosomes
  • Runx1 protein, mouse
  • Transcription Factors

Grant support

This work was supported by a grant from the Canadian Institutes of Health Research ( [MOP 62841 to A.P.M]; from the Canada Fund for Innovation Leaders Opportunity/Ontario Research Foundation ( [22880 to I.I.]; and from the National Science and Engineering Research Council ( [GPIN/372240-2009 to I.I.]. A.W. is supported by an Ontario Graduate Scholarship ( A.P.M. is a Canada Research Chair in Innate Pathogen Resistance ( The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.