Title

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

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Cell Biology

Date

3-30-2001

Document Type

Article

Medical Subject Headings

3T3 Cells; Animals; Cell Cycle; DNA-Binding Proteins; Histones; Interferon Regulatory Factor-1; Interferon Regulatory Factor-3; Interferon Regulatory Factor-7; Mice; Phosphoproteins; Signal Transduction; Trans-Activation (Genetics); Transcription Factors

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Interferon regulatory factors (IRFs) are transcriptional mediators of interferon-responsive signaling pathways that are involved in antiviral defense, immune response, and cell 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 up-regulation 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.

Rights and Permissions

Citation: J Biol Chem. 2001 May 25;276(21):18624-32. Epub 2001 Feb 13. Link to article on publisher's site

Related Resources

Link to Article in PubMed

PubMed ID

11278666