In:
Journal of Experimental Medicine, Rockefeller University Press, Vol. 214, No. 5 ( 2017-05-01), p. 1471-1491
Abstract:
TLR7/9 signals are capable of mounting massive interferon (IFN) response in plasmacytoid dendritic cells (pDCs) immediately after viral infection, yet the involvement of epigenetic regulation in this process has not been documented. Here, we report that zinc finger CXXC family epigenetic regulator CXXC5 is highly expressed in pDCs, where it plays a crucial role in TLR7/9- and virus-induced IFN response. Notably, genetic ablation of CXXC5 resulted in aberrant methylation of the CpG-containing island (CGI) within the Irf7 gene and impaired IRF7 expression in steady-state pDCs. Mechanistically, CXXC5 is responsible for the recruitment of DNA demethylase Tet2 to maintain the hypomethylation of a subset of CGIs, a process coincident with active histone modifications and constitutive transcription of these CGI-containing genes. Consequently, CXXC5-deficient mice had compromised early IFN response and became highly vulnerable to infection by herpes simplex virus and vesicular stomatitis virus. Together, our results identify CXXC5 as a novel epigenetic regulator for pDC-mediated antiviral response.
Type of Medium:
Online Resource
ISSN:
0022-1007
,
1540-9538
DOI:
10.1084/jem.20161149
Language:
English
Publisher:
Rockefeller University Press
Publication Date:
2017
detail.hit.zdb_id:
1477240-1
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