Role of PU.1 in MHC class II expression through transcriptional regulation of class II transactivator pI in dendritic cells

Kitamura, Nao; Yokoyama, Hokuto; Yashiro, Takashi; Nakano, Nobuhiro; Nishiyama, Makoto; Kanada, Shunsuke; Fukai, Tatsuo; Hara, Mutsuko; Ikeda, Shigaku; Ogawa, Hideoki; Okumura, Ko; Nishiyama, Chiharu

doi:10.1016/j.jaci.2011.10.019

Cited by 47 publications

(66 citation statements)

References 36 publications

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“…Chromatin immunoprecipitation (ChIP) assays were performed as described in our previous reports (5,34). Anti-FLAG tag mAb (M2) purchased from Sigma-Aldrich was used for immunoprecipitation, and mouse IgG (Life Technologies) was used as a control Ab.…”

Section: Chromatin Immunoprecipitation Assaymentioning

confidence: 99%

The Transcription Factor Ehf Is Involved in TGF-β–Induced Suppression of FcεRI and c-Kit Expression and FcεRI-Mediated Activation in Mast Cells

Yamazaki

Nakano

Honjo

et al. 2015

The Journal of Immunology

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FcεRI, which is composed of α, β, and γ subunits, plays an important role in IgE-mediated allergic responses. TGF-β1 has been reported to suppress FcεRI and stem cell factor receptor c-Kit expression on mast cell surfaces and to suppress mast cell activation induced by cross-linking of FcεRI. However, the molecular mechanism by which these expressions and activation are suppressed by TGF-β1 remains unclear. In this study, we found that the expression of Ets homologous factor (Ehf), a member of the Ets family transcriptional factors, is upregulated by TGF-β/Smad signaling in mouse bone marrow–derived mast cells (BMMCs). Forced expression of Ehf in BMMCs repressed the transcription of genes encoding FcεRIα, FcεRIβ, and c-Kit, resulting in a reduction in cell surface FcεRI and c-Kit expression. Additionally, forced expression of Ehf suppressed FcεRI-mediated degranulation and cytokine production. Ehf inhibited the promoter activity of genes encoding FcεRIα, FcεRIβ, and c-Kit by binding to these gene promoters. Furthermore, the mRNA levels of Gata1, Gata2, and Stat5b were lower in BMMCs stably expressing Ehf compared with control cells. Because GATA-1 and GATA-2 are positive regulators of FcεRI and c-Kit expression, decreased expression of GATAs may be also involved in the reduction of FcεRI and c-Kit expression. Decreased expression of Stat5 may contribute to the suppression of cytokine production by BMMCs. In part, mast cell response to TGF-β1 was mimicked by forced expression of Ehf, suggesting that TGF-β1 suppresses FcεRI and c-Kit expression and suppresses FcεRI-mediated activation through upregulation of Ehf.

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Section: Chromatin Immunoprecipitation Assaymentioning

confidence: 99%

The Transcription Factor Ehf Is Involved in TGF-β–Induced Suppression of FcεRI and c-Kit Expression and FcεRI-Mediated Activation in Mast Cells

Yamazaki

Nakano

Honjo

et al. 2015

The Journal of Immunology

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“…Extraction of total RNA from cells and reverse transcription to synthesize cDNA were performed, as described previously (15). The amount of mRNA for PU.1, GATA1, GATA2, and FcεRIa, b, and g was determined using a Step-One Real Time PCR system (Applied Biosystems) with TaqMan gene expression systems (Hs02786711_m1 for SPI1 [PU.1], Hs01085823_m1 for GATA1, Hs00231119_m1 for GATA2, Hs00758600 for FCERIA [FcεRIa], Hs00999628 for MS4A2 [FcεRIb], Hs00175408 for FcεRIg, and Hs00174029_m1 for c-kit) and TaqMan Universal Master Mix (Applied Biosystems).…”

Section: Quantification Of Mrna By Real-time Pcrmentioning

confidence: 99%

“…The ChIP assay was performed as described in our previous reports (7,15,17). Anti-PU.1 (T21, sc352), anti-GATA1 (N6, sc-265), and anti-GATA2 (H-116, sc-9008) Abs purchased from Santa Cruz Biotechnology (Santa Cruz, CA) were used for immunoprecipitation, and rat IgG (BD Biosciences) and rabbit IgG (02-6102; Invitrogen) were used as control Abs.…”

Section: Chip Assaymentioning

confidence: 99%

“…EMSA was performed, as described previously (14,15,17,18). Abs against GATA1, GATA2, and the control Abs were same as those used in the ChIP assay.…”

Section: Emsamentioning

confidence: 99%

“…The above results suggest that GATA2, which is recruited to the promoter region, transactivates the MS4A2 promoter directly. To evaluate the effects of GATA2 on MS4A2 promoter activity, we performed a reporter assay using HEK293T cells, because nonhematopoietic cell lines are useful for evaluating the transactivating activity of hematopoietic cell-specific transcription factors in coexpression analysis (7,15,17). Luciferase activity driven by the 2783/+33 region of the MS4A2 promoter was markedly upregulated by GATA2 coexpression, whereas the effect of coexpressed GATA1 on this promoter activity was low (Fig.…”

Section: Gata2 Transactivates the Human Ms4a2 Promoter Through Directmentioning

confidence: 99%

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Critical Roles for PU.1, GATA1, and GATA2 in the Expression of Human FcεRI on Mast Cells: PU.1 and GATA1 Transactivate FCER1A, and GATA2 Transactivates FCER1A and MS4A2

Inage

Kasakura

Yashiro

et al. 2014

The Journal of Immunology

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The high-affinity IgE receptor, FcεRI, which is composed of α-, β-, and γ-chains, plays an important role in IgE-mediated allergic responses. In the current study, involvement of the transcription factors, PU.1, GATA1, and GATA2, in the expression of FcεRI on human mast cells was investigated. Transfection of small interfering RNAs (siRNAs) against PU.1, GATA1, and GATA2 into the human mast cell line, LAD2, caused significant downregulation of cell surface expression of FcεRI. Quantification of the mRNA levels revealed that PU.1, GATA1, and GATA2 siRNAs suppressed the α transcript, whereas the amount of β mRNA was reduced in only GATA2 siRNA transfectants. In contrast, γ mRNA levels were not affected by any of the knockdowns. Chromatin immunoprecipitation assay showed that significant amounts of PU.1, GATA1, and GATA2 bind to the promoter region of FCER1A (encoding FcεRIα) and that GATA2 binds to the promoter of MS4A2 (encoding FcεRIβ). Luciferase assay and EMSA showed that GATA2 transactivates the MS4A2 promoter via direct binding. These knockdowns of transcription factors also suppressed the IgE-mediated degranulation activity of LAD2. Similarly, all three knockdowns suppressed FcεRI expression in primary mast cells, especially PU.1 siRNA and GATA2 siRNA, which target FcεRIα and FcεRIβ, respectively. From these results, we conclude that PU.1 and GATA1 are involved in FcεRIα transcription through recruitment to its promoter, whereas GATA2 positively regulates FcεRIβ transcription. Suppression of these transcription factors leads to downregulation of FcεRI expression and IgE-mediated degranulation activity. Our findings will contribute to the development of new therapeutic approaches for FcεRI-mediated allergic diseases.

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Transcriptional regulation of basophil‐specific protease genes by C/EBPα, GATA2, TGF‐β signaling, and epigenetic mechanisms

Tojima,

Nagata,

Ito

et al. 2024

FEBS Letters

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Basophils and mast cells (MCs) play an important role in immune responses against allergens and parasitic infection. To elucidate the mechanisms that determine the commitment between basophils and mast cell (MCs), transcription factors and epigenetic modifications regulating the gene expression of basophil‐specific enzymes, Mcpt8 and Mcpt11, were analyzed using bone marrow‐derived (BM) cells containing basophils and MCs. Knockdown (KD) and overexpression experiments revealed that the transcription factor C/EBPα positively regulated the gene expression of Mcpt8 and Prss34 (encoding Mcpt11). Cebpa, Mcpt8, and Prss34 mRNAs levels were upregulated by histone deacetylases and downregulated by DNA methyltransferases. Gata2 KD significantly reduced the mRNA levels of Mcpt8 and Prss34, while TGF‐β treatment increased those of Mcpt8 and Prss34. These results show that basophil‐specific protease genes were transactivated by C/EBPα, GATA2, and TGF‐β signaling and modified with epigenetic regulation.

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Role of PU.1 in MHC class II expression through transcriptional regulation of class II transactivator pI in dendritic cells

Cited by 47 publications

References 36 publications

The Transcription Factor Ehf Is Involved in TGF-β–Induced Suppression of FcεRI and c-Kit Expression and FcεRI-Mediated Activation in Mast Cells

The Transcription Factor Ehf Is Involved in TGF-β–Induced Suppression of FcεRI and c-Kit Expression and FcεRI-Mediated Activation in Mast Cells

Critical Roles for PU.1, GATA1, and GATA2 in the Expression of Human FcεRI on Mast Cells: PU.1 and GATA1 Transactivate FCER1A, and GATA2 Transactivates FCER1A and MS4A2

Transcriptional regulation of basophil‐specific protease genes by C/EBPα, GATA2, TGF‐β signaling, and epigenetic mechanisms

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