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

Nucleic Acids Research
Christopher D ScharerJeremy M Boss

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 ...Continue Reading

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Citations

Jun 14, 2017·European Journal of Immunology·David A AndersonKenneth M Murphy
Dec 31, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Muyao GuoChristopher D Scharer
Sep 21, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Robert R HainesJeremy M Boss
Feb 1, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Pietro CrivelloStefan Heinrichs
Jun 16, 2017·Scientific Reports·Alfonso Rodríguez-GilM Lienhard Schmitz
Mar 20, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jing HouPin Nie
Nov 23, 2019·The Journal of Experimental Medicine·Parimal MajumderJeremy M Boss
Dec 6, 2020·Immunological Reviews·Keenan J Wiggins, Christopher D Scharer
Jan 28, 2021·International Journal of Molecular Sciences·Jorge Alfonso León Machado, Viktor Steimle

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Datasets Mentioned

BETA
GSE52941
GSE52491
GM12878

Methods Mentioned

BETA
ChIP-chip
transgenic
ChIP-seq
FACS
immunoprecipitation
ChIP
PCR
immunoprecipitations
fluorescence-activated cell sorting
flow cytometry

Software Mentioned

UCSC Genome Browser
Bioconductor
R
MEME
HOMER R and Perl scripts
rtracklayer
Bowtie
bigWig
HOMER
CIITA

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