Ordered Recruitment of Chromatin Modifying and General Transcription Factors to the IFN-β Promoter

Abstract

Here, we show that the IFN-beta enhanceosome activates transcription by directing the ordered recruitment of chromatin modifying and general transcription factors to the IFN-beta promoter. The enhanceosome is assembled in the nucleosome-free enhancer region of the IFN-beta gene, leading to the modification and remodeling of a strategically positioned nucleosome that masks the TATA box and the start site of transcription. Initially, the GCN5 complex is recruited, which acetylates the nucleosome, and this is followed by recruitment of the CBP-PolII holoenzyme complex. Nucleosome acetylation in turn facilitates SWI/SNF recruitment by CBP, resulting in chromatin remodeling. This program of recruitment culminates in the binding of TFIID to the promoter and the activation of transcription.

IRF-3-dependent and augmented target genes during viral infection

“…21 In contrast, IRF-3 is required but not sufficient to induce expression of the IFN-b gene. 9,20,21 IRF-3 independent and augmented direct response genes Viral infection also stimulated the expression of direct response genes in the absence of IRF-3 (Supplementary Table 10). Although expression of this set of genes was independent of IRF-3, evaluation of the comparative levels of gene expression in the WT or KO cells revealed two distinct classes.…”

“…[16][17][18][19] IRF-3 contributes to the induction of the IFN-b gene, but it is not sufficient for IFN-b gene induction and needs to cooperate in an enhanceosome with NF-kB and ATF-2/c-jun transcription factors. 20 IFN is secreted by the infected cell and binds to cell surface receptors on the same cell or adjacent cells stimulating a signal pathway that induces expression of IFN-stimulated genes. IFN-receptor binding activates Janus tyrosine kinases that phosphorylate the DNA-binding transcription factors, signal trans ducers and activators of transcription (STAT).…”

Members of the hSWI/SNF chromatin remodeling complex associate with and are phosphorylated by protein kinase B/Akt

“…The hSWI/SNF complex also regulates a diverse group of other mammalian target genes. Chromatin immunoprecipitation experiments have demonstrated the presence of hSWI/SNF components on the promoters of IFNgand IFNa-inducible genes, as well as on the IFNb promoter (Agalioti et al, 2000;Huang et al, 2002;Liu et al, 2002;Pattenden et al, 2002;Cui et al, 2004). hSWI/SNF is also present on the CD44 and E-cadherin promoters (Banine et al, 2005;Gresh et al, 2005), on the promoters for myogenin and muscle creatine kinase (Simone et al, 2004), and on steroid receptor targets (Fryer and Archer, 1998;DiRenzo et al, 2000;Belandia et al, 2002;Me´tivier et al, 2003;Link et al, 2005).…”

“…The chromatin remodeling ability of hSWI/SNF has been shown to respond to various signaling pathways, including response to phosphoinositols (Zhao et al, 1998;Rando et al, 2002), the p38 pathway during skeletal myogenesis (Simone et al, 2004), interferons (Agalioti et al, 2000;Huang et al, 2002;Liu et al, 2002;Cui et al, 2004) and nuclear hormone receptors (Fryer and Archer, 1998;DiRenzo et al, 2000;Belandia et al, 2002;Me´tivier et al, 2003;Link et al, 2005). Phosphatidyl inositol 4,5-bisphosphate (PIP 2 ) has been shown to help increase the association of the SWI/SNF complex with the nuclear matrix (Zhao et al, 1998;Rando et al, 2002).…”

The Epigenetic Landscape of Lineage Choice: Lessons From the Heritability of Cd4 and Cd8 Expression

“…It has long been known that functional DNA elements are hypersensitive to endonucleases, and such DNase I hypersensitive sites (DHS) (Wu et al, 1979) occur upon nucleosome depletion. Studies of IFNβ gene activation during viral infection revealed that a nucleosome masking the transcription start site (TSS) and TATA box was remodeled by the histone acetylationrecruited SWI/SNF chromatin remodeling complex, allowing for TFIID recruitment (Agalioti et al, 2000). Binding of the TFIID subunit TBP to the TATA box induced the nucleosome to slide further downstream, exposing the transcription start site and allowing for transcription (Lomvardas and Thanos, 2001).…”