Chen, Yixiang, Wright, Jordan L., Meng, Xueqiong and Leppard, Keith (2015) Promyelocytic leukemia protein isoform II promotes transcription factor recruitment to activate interferon β and interferon-responsive gene expression. Molecular and Cellular Biology, Volume 35 (Number 10). pp. 1660-1672. doi:10.1128/MCB.01478-14 ISSN 0270-7306.

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Abstract

To trigger type I interferon (IFN) responses, pattern recognition receptors activate signaling cascades that lead to transcription of IFN and IFN-stimulated genes (ISGs). The promyelocytic leukaemia (PML) protein has been implicated in these responses though its role has not been defined. Here, we show that PML isoform II (PML-II) is specifically required for efficient induction of IFNβ transcription and of numerous ISGs, acting at the point of transcriptional complex assembly on target gene promoters. PML-II associated with specific transcription factors NF-κB and STAT1, as well as the co-activator CREB-binding protein (CBP), to facilitate transcriptional complex formation. The absence of PML-II substantially reduced binding of these factors and IRF3 to IFNβ or ISGs promoters and sharply reduced gene activation. The unique C-terminal exon of PML-II was essential for its activity while the N-terminal RBCC motif common to all PML isoforms was dispensable. We propose a model in which PML-II contributes to the transcription of multiple genes via the association of its C-terminal domain with relevant transcription complexes, which promotes the stable assembly of these complexes at promoters/enhancers of target genes and that in this way PML-II plays a significant role in the development of type I IFN responses.

Item Type:	Journal Article
Subjects:	Q Science > QH Natural history > QH301 Biology Q Science > QR Microbiology > QR180 Immunology
Divisions:	Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH):	Leukemia -- Genetic aspects, Leukemia -- Immunological aspects
Journal or Publication Title:	Molecular and Cellular Biology
Publisher:	American Society for Microbiology
ISSN:	0270-7306
Official Date:	May 2015
Dates:	Date Event May 2015 Published 2 March 2015 Available 23 February 2015 Accepted 10 December 2014 Submitted
Volume:	Volume 35
Number:	Number 10
Number of Pages:	13
Page Range:	pp. 1660-1672
DOI:	10.1128/MCB.01478-14
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Date of first compliant deposit:	27 April 2016
Date of first compliant Open Access:	27 April 2016
Funder:	Wellcome Trust (London, England), University of Warwick Postgraduate Research Scholarship, Great Britain-China Educational Trust, Sir Richard Stapley Educational Trust
Grant number:	WT094713MA (WT)

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