Apical role for BRG1 in cytokine-induced promoter assembly

Ni, Zuyao; Karaskov, Elizabeth; Tao, Yu; Callaghan, Steven M.; Der, Sandy D.; Park, David; Xu, Zhaodong; Pattenden, Samantha G.; Bremner, Rod

doi:10.1073/pnas.0503070102

Cited by 88 publications

(120 citation statements)

References 55 publications

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“…1A for significant effects of IFN-g). These data fit our prior findings that IFN-g induces recruitment of the histone acetyl transferases CBP and p300 to CIITA (11,19). Thus, in the pres- BRG1 alters positive and negative chromatin marks to poise CIITA for IFN-g induction Next, we examined these findings in another cell type and assessed whether BRG1 affects H3K27 modification at CIITA.…”

Section: Polycomb Repressive Complex 2 Marks Intraenhancer Domains Atsupporting

confidence: 67%

“…4B). As expected, siSUZ12 had a marginal effect on IRF1, a BRG1-independent IFN-g stimulated gene (7,11). Restoration of CIITA induction was not an off-target effect, because a distinct siSUZ12 also rescued IFN-g responsiveness (Supplemental Fig.…”

Section: Prc2 Confers Brg1 Dependency On Ciitamentioning

confidence: 68%

“…Next, we examined whether IFN-g treatment affects the PRC2 signature. Robust CIITA induction is detected 6 h after IFN-g treatment (7,11); at this time, we observed ∼4-fold less H3K27me3 at CIITA pIV and the 28-kb enhancer and ∼2-fold less H3K27me3 at the 22-kb, 213-kb, and 270-kb regions (see "*" in Fig. 2 for significant effects of IFN-g).…”

Section: Polycomb Repressive Complex 2 Marks Intraenhancer Domains Atmentioning

confidence: 85%

“…Thus, in the pres- BRG1 alters positive and negative chromatin marks to poise CIITA for IFN-g induction Next, we examined these findings in another cell type and assessed whether BRG1 affects H3K27 modification at CIITA. For this, we turned to BRG1-deficient SW-13 adrenal carcinoma cells, which were transduced with Ad-GFP or Ad-BRG1; physiological levels of the latter protein rescue IFN-g stimulated gene responsiveness at multiple BRG1-dependent genes (11).…”

Section: Polycomb Repressive Complex 2 Marks Intraenhancer Domains Atmentioning

confidence: 99%

“…BRG1 is dispensable for IFN-g-induced STAT1 recruitment to the IRF1 promoter and for IRF1 induction, but it is essential for subsequent recruitment of STAT1 and IRF1 proteins to CIITA pIV (11). SWI/SNF is also required for chromatin access and induction at several other IFN-g genes, activation of numerous IFN-a targets by the STAT1-STAT3-IRF9 trimer, and for STAT3-mediated upregulation of IL-6 gene targets, indicating a broad role for this chromatin-remodeling enzyme in cytokine signaling (11)(12)(13)(14)(15)(16).…”

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confidence: 99%

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Polycomb Repressive Complex 2 Confers BRG1 Dependency on the CIITA Locus

Hassan

Tao

Liu

et al. 2015

The Journal of Immunology

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CIITA (or MHC2TA) coordinates constitutive and IFN-γ–induced expression of MHC class II genes. IFN-γ responsiveness of CIITA requires BRG1 (SMARCA4), the ATPase engine of the chromatin remodeling SWI/SNF complex (also called BAF). SWI/SNF is defective in many human cancers, providing a mechanism to explain IFN-γ resistance. BRG1 dependency is mediated through remote elements. Short CIITA reporters lacking these elements respond to IFN-γ, even in BRG1-deficient cells, suggesting that BRG1 counters a remote repressive influence. The nature of this distal repressor is unknown, but it would represent a valuable therapeutic target to reactivate IFN-γ responsiveness in cancer. In this article, we show that the polycomb repressive complex 2 (PRC2) components EZH2 and SUZ12, as well as the associated histone mark H3K27me3, are codetected at interenhancer regions across the CIITA locus. IFN-γ caused a BRG1-dependent reduction in H3K27me3, associated with nucleosome displacement. SUZ12 knockdown restored IFN-γ responsiveness in BRG1-null cells, and it mimicked the ability of BRG1 to induce active histone modifications (H3K27ac, H3K4me) at the −50-kb enhancer. Thus, PRC2 confers BRG1 dependency on the CIITA locus. Our data suggest that, in addition to its known roles in promoting stemness and proliferation, PRC2 may inhibit immune surveillance, and it could be targeted to reactivate CIITA expression in SWI/SNF deficient cancers.

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Section: Polycomb Repressive Complex 2 Marks Intraenhancer Domains Atsupporting

confidence: 67%

Section: Prc2 Confers Brg1 Dependency On Ciitamentioning

confidence: 68%

Section: Polycomb Repressive Complex 2 Marks Intraenhancer Domains Atmentioning

confidence: 85%

Section: Polycomb Repressive Complex 2 Marks Intraenhancer Domains Atmentioning

confidence: 99%

mentioning

confidence: 99%

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Polycomb Repressive Complex 2 Confers BRG1 Dependency on the CIITA Locus

Hassan

Tao

Liu

et al. 2015

The Journal of Immunology

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The IFN‐γ‐induced transcriptional program of the CIITA gene is inhibited by statins

2008

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Statins are 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors that exert anti-inflammatory effects. IFN-c induction of class II MHC expression, which requires the class II transactivator (CIITA), is inhibited by statins; however, the molecular basis for suppression is undetermined. We describe that statins inhibit IFN-c-induced class II MHC expression by suppressing CIITA gene expression, which is dependent on the HMG-CoA reductase pathway. In addition, CIITA expression is inhibited by GGTI-298 or Clostridium difficile Toxin A, specific inhibitors of Rho family protein prenylation, indicating the involvement of small GTPases. Rac1 is involved in IFN-c inducible expression of CIITA, and statins inhibit IFN-c-induced Rac1 activation, contributing to the inhibitory effect of statins. IFN-c induction of the CIITA gene is regulated by the transcription factors STAT-1a, interferon regulatory factor (IRF)-1 and upstream stimulatory factor (USF)-1. We previously reported that statins inhibit constitutive STAT-1a expression. IRF-1, a STAT-1 dependent gene, is also inhibited by statins. Therefore, statin treatment results in decreased recruitment of STAT-1a and IRF-1 to the endogenous CIITA promoter IV (pIV). The recruitment of USF-1 to CIITA pIV is also reduced by statins, as is the recruitment of RNA polymerase II (Pol II), p300 and Brg-1. These data indicate that statins inhibit the transcriptional program of the CIITA gene.

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Induction of Samhd1 by interferon gamma and lipopolysaccharide in murine macrophages requires IRF1

et al. 2020

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SAMHD1 is an enzyme with phosphohydrolase activity. Mutations in SAMHD1 have been linked to the development of Aicardi‐Goutières syndrome in humans. This enzyme also has the capacity to restrict HIV virus replication in macrophages. Here, we report that Samhd1 is highly expressed in murine macrophages and is regulated by proinflammatory (IFN‐γ and LPS) but not by anti‐inflammatory (IL‐4 or IL‐10) activators. The induction of Samhd1 follows the pattern of an intermediate gene that requires protein synthesis. In transient transfection experiments using the Samhd1 promoter, we found that a fragment of 27 bps of this gene, falling between −937 and −910 bps relative to the transcription start site, is required for IFN‐γ‐dependent activation. Using EMSAs, we determined that IFN‐γ treatment led to the elimination of a protein complex. Chromatin immunoprecipitation assays and siRNA experiments revealed that IRF1 is required for IFN‐γ‐ or LPS‐induced Samhd1 expression. Therefore, our results indicate that Samhd1 is stimulated by proinflammatory agents IFN‐γ and LPS. Moreover, they reveal that these two agents, via IRF1, eliminate a protein complex that may be related to a repressor, thereby, triggering Samhd1 expression.

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Apical role for BRG1 in cytokine-induced promoter assembly

Cited by 88 publications

References 55 publications

Polycomb Repressive Complex 2 Confers BRG1 Dependency on the CIITA Locus

Polycomb Repressive Complex 2 Confers BRG1 Dependency on the CIITA Locus

The IFN‐γ‐induced transcriptional program of the CIITA gene is inhibited by statins

Induction of Samhd1 by interferon gamma and lipopolysaccharide in murine macrophages requires IRF1

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