title: Nucleosome Presence at AML-1 Binding Sites Inversely Correlates with Ly49 Expression: Revelations from an Informatics Analysis of Nucleosomes and Immune Cell Transcription Factors.
abstract: 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.
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Andrew
authors.identifier: 0000-0003-3116-8722
authors.initials: A
authors.lastname: Wight
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.|Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Doo
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.|Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Ilya
authors.initials: I
authors.lastname: Ioshikhes
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.|Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Makrigiannis
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D002874:Chromosome Mapping; D019295:Computational Biology; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D051379:Mice; D005810:Multigene Family; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000235:genetics*; D009707:Nucleosomes / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D055650:NK Cell Lectin-Like Receptor Subfamily A; D009707:Nucleosomes; C493726:Runx1 protein, mouse; D014157:Transcription Factors