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

Ronglin Xie, Andre J van Wijnen, Caroline Van Der Meijden, Mai X. Luong, Janet L. Stein, Gary S. Stein

Research output: Contribution to journalArticle

33 Citations (Scopus)

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 γ 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.

Original languageEnglish (US)
Pages (from-to)18624-18632
Number of pages9
JournalJournal of Biological Chemistry
Volume276
Issue number21
DOIs
StatePublished - Jan 25 2001
Externally publishedYes

Fingerprint

Interferon Regulatory Factor-7
Interferon Regulatory Factor-3
Interferon Regulatory Factors
Interferon Regulatory Factor-1
Interferon Regulatory Factor-2
Transcription
Cell Cycle Checkpoints
Histones
Genes
Cells
Up-Regulation
Reporter Genes
Gene expression
Interferons
Gene Expression
Cell growth
Growth
Luciferases
Antiviral Agents
Transfection

ASJC Scopus subject areas

  • Biochemistry

Cite this

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. / Xie, Ronglin; van Wijnen, Andre J; Van Der Meijden, Caroline; Luong, Mai X.; Stein, Janet L.; Stein, Gary S.

In: Journal of Biological Chemistry, Vol. 276, No. 21, 25.01.2001, p. 18624-18632.

Research output: Contribution to journalArticle

Xie, Ronglin ; van Wijnen, Andre J ; Van Der Meijden, Caroline ; Luong, Mai X. ; Stein, Janet L. ; Stein, Gary S. / 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. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 21. pp. 18624-18632.
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AU - van Wijnen, Andre J

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