Distinct Modes of Action Applied by Transcription Factors STAT1 and IRF1 to Initiate Transcription of the IFN-gamma-inducible Gbp2 Gene

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2007 Feb 13

PMID 17293456

Citations 74

Authors

Katrin Ramsauer

Matthias Farlik

Gordin Zupkovitz

Christian Seiser

Andrea Kroger

Hansjorg Hauser

Thomas Decker

Affiliations

Soon will be listed here.

Abstract

A subgroup of genes induced by IFN-gamma requires both STAT1 and IRF1 for transcriptional activation. Using WT, stat1(-/-), or irf1(-/-) cells, we analyzed the changes induced by IFN-gamma in gbp2 promoter chromatin. STAT1 associated with the promoter independently of IRF1 and played an essential role in the ordered recruitment of the coactivator/histone acetyl transferase CREB-binding protein (CBP) and the histone deacetylase HDAC1. Hyperacetylation of histone 4 also required STAT1. Phosphorylation at S727 in the transactivating domain increased transcriptional activity of STAT1. In cells expressing a STAT1S727A-mutant CBP recruitment, histone 4 hyperacetylation and RNA polymerase II association with the gbp2 promoter were strongly reduced. IRF1 association with the gbp2 promoter followed that of STAT1, but STAT1 association with DNA or histone hyperacetylation were not necessary for IRF1 binding. RNA polymerase II association with the gbp2 promoter required both STAT1 and IRF1, suggesting that both proteins mediate essential steps in transcriptional activation. IRF1, but not STAT1, was found to coimmunoprecipitate with RNA polymerase II. Together, the data support the assumption that the main role of STAT1 in activating gbp2 transcription is to provide transcriptionally competent chromatin, whereas the function of IRF1 may lie in directly contacting RNA polymerase II-containing transcriptional complexes.

Citing Articles

Analysis of the Transcriptional Control of in Chicken: IRF1 and GATA1 as Negative Regulators.

Qiu L, Wang H, Li W, Yang T, Bai H, Chang G Animals (Basel). 2025; 15(5).

PMID: 40075948 PMC: 11898421. DOI: 10.3390/ani15050665.

P300/RNA polymerase II mediates induction of the teleost viral RNA sensor MDA5 through the interferon regulatory factor IRF11.

Li W, Feng Y, Teng Y, Montero A, Zhou Y, Zhang X J Biol Chem. 2025; 301(2):108193.

PMID: 39826689 PMC: 11849104. DOI: 10.1016/j.jbc.2025.108193.

INHBA promotes tumor growth and induces resistance to PD-L1 blockade by suppressing IFN-γ signaling.

Li F, Gu L, Tong Y, Chen R, Chen S, Yu X Acta Pharmacol Sin. 2024; 46(2):448-461.

PMID: 39223366 PMC: 11747416. DOI: 10.1038/s41401-024-01381-x.

Dynamic control of gene expression by ISGF3 and IRF1 during IFNβ and IFNγ signaling.

Ravi Sundar Jose Geetha A, Fischer K, Babadei O, Smesnik G, Vogt A, Platanitis E EMBO J. 2024; 43(11):2233-2263.

PMID: 38658796 PMC: 11148166. DOI: 10.1038/s44318-024-00092-7.

Cooperative interaction of interferon regulatory factor -1 and bromodomain-containing protein 4 on RNA polymerase activation for intrinsic innate immunity.

Xu X, Qiao D, Brasier A Front Immunol. 2024; 15:1366235.

PMID: 38601157 PMC: 11004252. DOI: 10.3389/fimmu.2024.1366235.

References

Lew D, Decker T, Strehlow I, Darnell J . Overlapping elements in the guanylate-binding protein gene promoter mediate transcriptional induction by alpha and gamma interferons. Mol Cell Biol. 1991; 11(1):182-91. PMC: 359608. DOI: 10.1128/mcb.11.1.182-191.1991. View

Pine R . Constitutive expression of an ISGF2/IRF1 transgene leads to interferon-independent activation of interferon-inducible genes and resistance to virus infection. J Virol. 1992; 66(7):4470-8. PMC: 241256. DOI: 10.1128/JVI.66.7.4470-4478.1992. View

Kirchhoff S, Schaper F, Hauser H . Interferon regulatory factor 1 (IRF-1) mediates cell growth inhibition by transactivation of downstream target genes. Nucleic Acids Res. 1993; 21(12):2881-9. PMC: 309674. DOI: 10.1093/nar/21.12.2881. View

Nicolet C, Paulnock D . Promoter analysis of an interferon-inducible gene associated with macrophage activation. J Immunol. 1994; 152(1):153-62. View

Pine R, Canova A, Schindler C . Tyrosine phosphorylated p91 binds to a single element in the ISGF2/IRF-1 promoter to mediate induction by IFN alpha and IFN gamma, and is likely to autoregulate the p91 gene. EMBO J. 1994; 13(1):158-67. PMC: 394789. DOI: 10.1002/j.1460-2075.1994.tb06245.x. View

Kimura T, Nakayama K, Penninger J, Kitagawa M, Harada H, Matsuyama T . Involvement of the IRF-1 transcription factor in antiviral responses to interferons. Science. 1994; 264(5167):1921-4. DOI: 10.1126/science.8009222. View

Reis L, Ruffner H, Stark G, Aguet M, Weissmann C . Mice devoid of interferon regulatory factor 1 (IRF-1) show normal expression of type I interferon genes. EMBO J. 1994; 13(20):4798-806. PMC: 395418. DOI: 10.1002/j.1460-2075.1994.tb06805.x. View

Briken V, Ruffner H, Schultz U, Schwarz A, Reis L, Strehlow I . Interferon regulatory factor 1 is required for mouse Gbp gene activation by gamma interferon. Mol Cell Biol. 1995; 15(2):975-82. PMC: 231988. DOI: 10.1128/MCB.15.2.975. View

Bluyssen H, Muzaffar R, Vlieststra R, van der Made A, Leung S, Stark G . Combinatorial association and abundance of components of interferon-stimulated gene factor 3 dictate the selectivity of interferon responses. Proc Natl Acad Sci U S A. 1995; 92(12):5645-9. PMC: 41753. DOI: 10.1073/pnas.92.12.5645. View

10.

Wen Z, Zhong Z, Darnell Jr J . Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation. Cell. 1995; 82(2):241-50. DOI: 10.1016/0092-8674(95)90311-9. View

11.

Durbin J, Hackenmiller R, Simon M, Levy D . Targeted disruption of the mouse Stat1 gene results in compromised innate immunity to viral disease. Cell. 1996; 84(3):443-50. DOI: 10.1016/s0092-8674(00)81289-1. View

12.

Wang I, Blanco J, Tsai S, Tsai M, Ozato K . Interferon regulatory factors and TFIIB cooperatively regulate interferon-responsive promoter activity in vivo and in vitro. Mol Cell Biol. 1996; 16(11):6313-24. PMC: 231634. DOI: 10.1128/MCB.16.11.6313. View

13.

Zhang J, Vinkemeier U, Gu W, Chakravarti D, Horvath C, Darnell Jr J . Two contact regions between Stat1 and CBP/p300 in interferon gamma signaling. Proc Natl Acad Sci U S A. 1996; 93(26):15092-6. PMC: 26361. DOI: 10.1073/pnas.93.26.15092. View

14.

Weihua X, Kolla V, Kalvakolanu D . Interferon gamma-induced transcription of the murine ISGF3gamma (p48) gene is mediated by novel factors. Proc Natl Acad Sci U S A. 1997; 94(1):103-8. PMC: 19246. DOI: 10.1073/pnas.94.1.103. View

15.

Kimura T, Kadokawa Y, Harada H, Matsumoto M, Sato M, Kashiwazaki Y . Essential and non-redundant roles of p48 (ISGF3 gamma) and IRF-1 in both type I and type II interferon responses, as revealed by gene targeting studies. Genes Cells. 1996; 1(1):115-24. DOI: 10.1046/j.1365-2443.1996.08008.x. View

16.

Muhlethaler-Mottet A, Di Berardino W, Otten L, MACH B . Activation of the MHC class II transactivator CIITA by interferon-gamma requires cooperative interaction between Stat1 and USF-1. Immunity. 1998; 8(2):157-66. DOI: 10.1016/s1074-7613(00)80468-9. View

17.

Kovarik P, Stoiber D, Novy M, Decker T . Stat1 combines signals derived from IFN-gamma and LPS receptors during macrophage activation. EMBO J. 1998; 17(13):3660-8. PMC: 1170702. DOI: 10.1093/emboj/17.13.3660. View

18.

Kretsovali A, Agalioti T, Spilianakis C, Tzortzakaki E, Merika M, Papamatheakis J . Involvement of CREB binding protein in expression of major histocompatibility complex class II genes via interaction with the class II transactivator. Mol Cell Biol. 1998; 18(11):6777-83. PMC: 109261. DOI: 10.1128/MCB.18.11.6777. View

19.

Anderson S, Carton J, Zhang X, Rubin B . Genomic organization and chromosomal localization of a new member of the murine interferon-induced guanylate-binding protein family. J Interferon Cytokine Res. 1999; 19(5):487-94. DOI: 10.1089/107999099313938. View

20.

Decker T, Kovarik P . Transcription factor activity of STAT proteins: structural requirements and regulation by phosphorylation and interacting proteins. Cell Mol Life Sci. 1999; 55(12):1535-46. PMC: 11146901. DOI: 10.1007/s000180050393. View