title: Inferring a role for methylation of intergenic DNA in the regulation of genes aberrantly expressed in precursor B-cell acute lymphoblastic leukemia.
abstract: A complete understanding of the mechanisms involved in the development of pre-B ALL is lacking. In this study, we integrated DNA methylation data and gene expression data to elucidate the impact of aberrant intergenic DNA methylation on gene expression in pre-B ALL. We found a subset of differentially methylated intergenic loci that were associated with altered gene expression in pre-B ALL patients. Notably, 84% of these regions were also bound by transcription factors (TF) known to play roles in differentiation and B-cell development in a lymphoblastoid cell line. Further, an overall downregulation of eRNA transcripts was observed in pre-B ALL patients and these transcripts were associated with the downregulation of putative target genes involved in B-cell migration, proliferation, and apoptosis. The identification of novel putative regulatory regions highlights the significance of intergenic DNA sequences and may contribute to the identification of new therapeutic targets for the treatment of pre-B ALL.
authors.affiliation: a Department of Pathology and Anatomical Sciences , University of Missouri-Columbia , Columbia , MO , USA.
authors.forename: Md
authors.initials: M
authors.lastname: Almamun
authors.affiliation: a Department of Pathology and Anatomical Sciences , University of Missouri-Columbia , Columbia , MO , USA.
authors.forename: Olha
authors.initials: O
authors.lastname: Kholod
authors.affiliation: a Department of Pathology and Anatomical Sciences , University of Missouri-Columbia , Columbia , MO , USA.
authors.forename: Alexei J
authors.initials: AJ
authors.lastname: Stuckel
authors.affiliation: a Department of Pathology and Anatomical Sciences , University of Missouri-Columbia , Columbia , MO , USA.
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Levinson
authors.affiliation: b Bioinformatics and Computational Biology , Worcester Polytechnic Institute , Worcester , MA , USA.
authors.forename: Nathan T
authors.initials: NT
authors.lastname: Johnson
authors.affiliation: a Department of Pathology and Anatomical Sciences , University of Missouri-Columbia , Columbia , MO , USA.
authors.forename: Gerald L
authors.initials: GL
authors.lastname: Arthur
authors.affiliation: c Department of Health Management and Informatics , University of Missouri-Columbia , Columbia , MO , USA.
authors.forename: J Wade
authors.initials: JW
authors.lastname: Davis
authors.affiliation: a Department of Pathology and Anatomical Sciences , University of Missouri-Columbia , Columbia , MO , USA.
authors.forename: Kristen H
authors.initials: KH
authors.lastname: Taylor
mesh_terms: D045744:Cell Line, Tumor; D019175:DNA Methylation; D021901:DNA, Intergenic; D004742:Enhancer Elements, Genetic; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D056426:Genetic Loci; D006801:Humans; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D022661:RNA, Untranslated
chemical_list: D021901:DNA, Intergenic; D022661:RNA, Untranslated
keywords: DNA methylation; acute lymphoblastic leukemia; eRNA; enhancer; precursor B-cell; transcription factor