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Title: Identification of a novel Aire-regulating cis-regulatory element using H3K27ac ChIP-seq      
keywords:
Epigenomics
ID:
PRJNA299575
description:
Thymic central tolerance is essential to preventing autoimmunity. In medullary thymic epithelial cells (mTECs), the Autoimmune regulator (Aire) gene plays an essential role in this process by driving the expression of a diverse set of tissue-specific antigens (TSAs), which are presented and help tolerize self-reactive thymocytes. Interestingly, Aire has a highly tissue-restricted pattern of expression, with only mTECs and peripheral extrathymic Aire-expressing cells (eTACs) known to express detectable levels in adults. Despite this high level of tissue specificity, the cis-regulatory elements that control Aire expression have remained obscure. We used sequence conservation analysis and ChIP-seq against the enhancer-associated histone mark H3K27ac to identify a candidate Aire cis-regulatory element. There is enrichment of H3K27ac near this element, ACNS1, in mTECs and the element also has characteristics of being NF-κB-responsive. Finally, we find that this element is essential for Aire expression in vivo and necessary to prevent spontaneous autoimmunity, reflecting the importance of this regulatory DNA element in promoting immune tolerance. Overall design: Two experimental groups (GFP neg mTECs and GFP pos mTECs), each with three samples, and one control sample (D10 Th2 cells).
accesstypes:
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA299575
authentication:
none
authorization:
none
ID:
pmid:26527800
name:
Mus musculus
ncbiID:
ncbitax:10090
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject
  • S10 OD016262/OD/NIH HHS/United States

  • P30 DK063720/DK/NIDDK NIH HHS/United States

  • T32 AI007334/AI/NIAID NIH HHS/United States

  • F30 DK100098/DK/NIDDK NIH HHS/United States

  • T32 GM007618/GM/NIGMS NIH HHS/United States

  • R01 DK101622/DK/NIDDK NIH HHS/United States

  • R01 HL114093/HL/NHLBI NIH HHS/United States

  • K12 HD072222/HD/NICHD NIH HHS/United States

  • R01 AI097457/AI/NIAID NIH HHS/United States

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