The POU transcription factor Oct-1 represses virus-induced interferon A gene expression.

Abstract:

:Alpha interferon (IFN-alpha) and IFN-beta are able to interfere with viral infection. They exert a vast array of biologic functions, including growth arrest, cell differentiation, and immune system regulation. This regulation extends from innate immunity to cellular and humoral adaptive immune responses. A strict control of expression is needed to prevent detrimental effects of unregulated IFN. Multiple IFN-A subtypes are coordinately induced in human and mouse cells infected by virus and exhibit differences in expression of their individual mRNAs. We demonstrated that the weakly expressed IFN-A11 gene is negatively regulated after viral infection, due to a distal negative regulatory element, binding homeoprotein pituitary homeobox 1 (Pitx1). Here we show that the POU protein Oct-1 binds in vitro and in vivo to the IFN-A11 promoter and represses IFN-A expression upon interferon regulatory factor overexpression. Furthermore, we show that Oct-1-deficient MEFs exhibit increased in vivo IFN-A gene expression and increased antiviral activity. Finally, the IFN-A expression pattern is modified in Oct-1-deficient MEFs. The broad representation of effective and potent octamer-like sequences within IFN-A promoters suggests an important role for Oct-1 in IFN-A regulation.

journal_name

Mol Cell Biol

authors

Mesplède T,Island ML,Christeff N,Petek F,Doly J,Navarro S

doi

10.1128/MCB.25.19.8717-8731.2005

subject

Has Abstract

pub_date

2005-10-01 00:00:00

pages

8717-31

issue

19

eissn

0270-7306

issn

1098-5549

pii

25/19/8717

journal_volume

25

pub_type

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