ATAC-seq on biobanked specimens defines a unique chromatin accessibility structure in naive SLE B cells

• Type of Material: Article
• Authors: Christopher Scharer, Emory University; Emily L. Blalock, Emory University; Benjamin G. Barwick, Emory University; Robert R. Haines, Emory University; Chungwen Wei, Emory University; Ignacio Sanz, Emory University; Jeremy Boss, Emory University
• Language: English
• Date: 2016-06-01
• Publisher: Nature Publishing Group
• Publication Version: Final Published Version
• Copyright Statement: © 2016, Macmillan Publishers Limited.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/srep27030
• Title of Journal or Parent Work: Scientific Reports
• ISSN: 2045-2322
• Volume: 6
• Start Page: 27030
• End Page: 27030
• Grant/Funding Information: Grants from the National Institutes of Health. B.G.B was supported by F31AI112261 and previously by T32GM008490. R.R.H was supported by T32GM008490. This work was funded by U19AI110483 to J.M.B and I.S. and RO1GM47310 to J.M.B.
• Keywords: SYSTEMIC-LUPUS-ERYTHEMATOSUS; MACROPHAGE; ENCODE; Epigenomics; DISEASE; Multidisciplinary Sciences; SIGNALING PATHWAYS; Autoimmunity; SUSCEPTIBILITY; EXPRESSION; TRANSCRIPTION FACTORS; LARGE GENE LISTS; POPULATION; Epigenetics
• Research Categories: Health Sciences, Immunology; Biology, Microbiology

Abstract

Biobanking is a widespread practice for storing biological samples for future studies ranging from genotyping to RNA analysis. However, methods that probe the status of the epigenome are lacking. Here, the framework for applying the Assay for Transposase Accessible Sequencing (ATAC-seq) to biobanked specimens is described and was used to examine the accessibility landscape of naïve B cells from Systemic Lupus Erythematosus (SLE) patients undergoing disease flares. An SLE specific chromatin accessibility signature was identified. Changes in accessibility occurred at loci surrounding genes involved in B cell activation and contained motifs for transcription factors that regulate B cell activation and differentiation. These data provide evidence for an altered epigenetic programming in SLE B cells and identify loci and transcription factor networks that potentially impact disease. The ability to determine the chromatin accessibility landscape and identify cis-regulatory elements has broad application to studies using biorepositories and offers significant advantages to improve the molecular information obtained from biobanked samples.