The cell cycle control element of histone H4 gene transcription is maximally responsive to interferon regulatory factor pairs IRF-1/IRF-3 and IRF-1/IRF-7

被引：34

作者：

Xie, RL ^{[1
]}

van Wijnen, AJ ^{[1
]}

van der Meijden, C ^{[1
]}

Luong, MX ^{[1
]}

Stein, JL ^{[1
]}

Stein, GS ^{[1
]}

机构：

[1] Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA 01655 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2001年 / 276卷 / 21期

关键词：

D O I：

10.1074/jbc.M010391200

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Interferon regulatory factors (IRFs) are transcriptional mediators of interferon-responsive signaling pathways that are involved in antiviral defense, immune response, and hell growth regulation. To investigate the role of IRF proteins in the regulation of histone H4 gene transcription, we compared the transcriptional contributions of IRF-1, IRF-2, IRF-3, and IRF-7 using transient transfection assays with H4 promoter/luciferase (Luc) reporter genes. These IRF proteins up-regulate reporter gene expression but IRF-1, IRF-3, and IRF-7 are more potent activators of the H4 promoter than IRF-2. Forced expression of different IRF combinations reveals that IRF-2 reduces IRF-1 or IRF-3 dependent activation, but does not affect IRF-7 function. Thus, IRF-2 may have a dual function in histone H4 gene transcription by acting as a weak activator at low dosage and a competitive inhibitor of other strongly activating IRFs at high levels. IRF-1/IRF-3 and IRF-1/IRF-7 pairs each mediate the highest levels of site II-dependent promoter activity and can up-regulate transcription by 120-150-fold. We also find that interferon gamma up-regulates IRF-1 and site II-dependent promoter activity. This upregulation is not observed when the IRF site is mutated or if cells are preloaded with IRF-1. Our results indicate that IRF-1, IRF-2, IRF-3, and IRF-7 can all regulate histone H4 gene expression. The pairwise utilization of distinct IRF factors provides a flexible transcriptional mechanism for integration of diverse growth-related signaling pathways.

引用

页码：18624 / 18632

页数：9

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