p300, but not PCAF, collaborates with IRF‐1 in stimulating TRIM22 expression independently of its histone acetyltransferase activity

Abstract

Tripartite motif (TRIM) 22 plays an important role in IFN-mediated antiviral activity.We previously demonstrated that IFN regulatory factor-1 (IRF-1) was crucial for constitutive and IFN-induced TRIM22 expression via binding to a special cis-element named 5 extended IFN-stimulating response element. Here, we further investigate the molecular mechanisms of TRIM22 with a focus on the co-activators of IRF-1. Using an in vitro DNA affinity binding assay and an in vivo chromatin immunoprecipitation assay, we found that IFN-γ stimulation significantly enhanced the binding of p300 and p300/CBPassociated factor, but not other co-activators such as general control nondepressible 5, steroid receptor co-activator-1, and activator of thyroid and retinoic, to the 5 extended IFN-stimulating response element containing TRIM22 promoter region together with IRF-1. Overexpression and knockdown analysis demonstrated that it was p300, but not p300/CBP-associated factor, that functioned as a transcriptional co-activator of IRF-1 in IFN-γ induction of TRIM22. We further show that p300 contributed to both IFN-γ-and IRF-1-mediated TRIM22 transcription independent of its histone acetyltransferase activity, however, it was required for the recruitment of RNA polymerase II to TRIM22 promoter region. These data indicate that p300 plays a critical role in IFN-γ-induced TRIM22 expression via recruiting RNA polymerase II to the TRIM22 promoter, and might serve as a bridge between IRF-1 and the basal transcriptional apparatus in TRIM22 induction.Keywords: Co-activator r Histone acetyltransferase activity r IFN r p300 r TRIM22 Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionTRIM22 is a member of the tripartite motif (TRIM) family proteins that are involved in a variety of biological processes, includCorrespondence: Dr. Sidong Xiong e-mail: sdxiongfd@126.com ing transcriptional regulation, apoptosis, immune signaling, and antiviral activities [1][2][3][4][5]. TRIM22 is demonstrated to be an IFN-inducible p53 target gene and may play an important role in cellular proliferation and differentiation [6,7]. It has also been linked to the activation of lymphocytes [8,9], and may play a role in autoimmune diseases [10]. Our previous investigation revealed that TRIM22 was a RING finger E3 ubiquitin ligase [11] and was involved in the activation of NF-κB [12]. However, TRIM22 With the aim of elucidating the molecular mechanisms whereby IFNs regulate TRIM22 expression, we previously identified a special cis-element named 5 extended IFN-stimulating response element (5 eISRE) that was crucial for IFN-γ-induced TRIM22 expression, and demonstrated that it was IFN regulatory factor-1 (IRF-1), not signal transducer and activator of transcription 1 (STAT1), that bound to this cis-element and played an indispensable role in this induction. Furthermore, the association of IRF-1 with 5 eISRE was also revealed to be important for TRIM22 induction by IFN-α, as well as for the constitutive ex...

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