Genome-wide CIITA-binding profile identifies sequence preferences that dictate function versus recruitment.

• Type of Material: Article
• Authors: Christopher Scharer, Emory University; Nancy M. Choi, Emory University; Benjamin Barwick, Emory University; Parimal Majumder, Emory University; Sarah Lohsen, Emory University; Jeremy Boss, Emory University
• Language: English
• Date: 2015-03-31
• Publisher: Oxford University Press (OUP): Policy C - Option B
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2015.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1093/nar/gkv182
• Title of Journal or Parent Work: Nucleic Acids Research
• ISSN: 0305-1048
• Volume: 43
• Issue: 6
• Start Page: 3128
• End Page: 3142
• Grant/Funding Information: National Institutes of Health [RO1 GM47310 to J.M.B., F31 AI112261-01 to B.G.B. and T32 support for S.L. and B.G.B. GM008490].; Funding for open access charge: National Institutes of Health [RO1 GM47310 to J.M.B., F31 AI112261-01 to B.G.B. and T32 support for S.L. and B.G.B. GM008490].
• Research Categories: Health Sciences, Immunology

Abstract

The class II transactivator (CIITA) is essential for the expression of major histocompatibility complex class II (MHC-II) genes; however, the role of CIITA in gene regulation outside of MHC-II biology is not fully understood. To comprehensively map CIITA-bound loci, ChIP-seq was performed in the human B lymphoblastoma cell line Raji. CIITA bound 480 sites, and was significantly enriched at active promoters and enhancers. The complexity of CIITA transcriptional regulation of target genes was analyzed using a combination of CIITA-null cells, including a novel cell line created using CRISPR/Cas9 tools. MHC-II genes and a few novel genes were regulated by CIITA; however, most other genes demonstrated either diminished or no changes in the absence of CIITA. Nearly all CIITA-bound sites were within regions containing accessible chromatin, and CIITA's presence at these sites was associated with increased histone H3K27 acetylation, suggesting that CIITA's role at these non-regulated loci may be to poise the region for subsequent regulation. Computational genome-wide modeling of the CIITA bound XY box motifs provided constraints for sequences associated with CIITA-mediated gene regulation versus binding. These data therefore define the CIITA regulome in B cells and establish sequence specificities that predict activity for an essential regulator of the adaptive immune response.