Functionally distinct Gata3/Chd4 complexes coordinately establish T helper 2 (Th2) cell identity

Hosokawa, Hiroyuki; Tanaka, Tomoaki; Suzuki, Yutaka; Iwamura, Chiaki; Ohkubo, Shinji; Endoh, Kanji; Kato, Mayumi; Endo, Yusuke; Onodera, Atsushi; Tumes, Damon J.; Kanai, Akinori; Sugano, Sumio; Nakayama, Toshinori

doi:10.1073/pnas.1220865110

Cited by 77 publications

(69 citation statements)

References 35 publications

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“…Multiple transcription factors including Miz-1 and GATA3 have been found to act as both a transcriptional activator and repressor. It was reported that whether they function as a transcriptional activator or a repressor depends on their interactions with other transcriptional regulators (32,33). Spi-B expression endows lung cancer cells with two properties that are normally required for expansion of developmentally mature B lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

Spi-B–Mediated Silencing of Claudin-2 Promotes Early Dissemination of Lung Cancer Cells from Primary Tumors

Niu

et al. 2017

Cancer Research

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Dissociation from epithelial sheets and invasion through the surrounding stroma are critical early events during epithelial cancer metastasis. Here we find that a lymphocyte lineage-restricted transcription factor, Spi-B, is frequently expressed in human lung cancer tissues. The Spi-B-expressing cancer cells coexpressed vimentin but repressed E-cadherin and exhibited invasive behavior. Increased Spi-B expression was associated with tumor grade, lymphatic metastasis, and short overall survival. Mechanistically, Spi-B disrupted intercellular junctions and enhanced invasiveness by reconfiguring the chromatin structure of the tight junction gene claudin-2 (CLDN2) and repressing its transcription. These data suggest that Spi-B participates in mesenchymal invasion, linking epithelial cancer metastasis with a lymphatic transcriptional program.

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Section: Discussionmentioning

confidence: 99%

Spi-B–Mediated Silencing of Claudin-2 Promotes Early Dissemination of Lung Cancer Cells from Primary Tumors

Niu

et al. 2017

Cancer Research

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“…Cell Clone, D10G4.1-FLAG-tagged Gata3 proteins were purified from D10G4.1 as described previously (18). The proteins were digested with trypsin.…”

Section: Identification Of the Methylation Sites Of Gata3 In The Th2mentioning

confidence: 99%

“…Immunoprecipitation and Immunoblotting-Immunoprecipitation was performed as described previously (18). After electrophoresis, the proteins were subjected to immunoblotting as described previously (37).…”

Section: Identification Of the Methylation Sites Of Gata3 In The Th2mentioning

confidence: 99%

“…The AP-1 transcription factor consists of a variety of dimers composed of members of the Fos, Jun, and activating transcription factor (ATF) families of proteins (39). Among the Jun family proteins, we previously found that JunB was a Gata3-interacting molecule in Th2 cells (18). Moreover, JunB was identified as one of the components of the transcriptional activation complex at the Il5 proximal promoter (40).…”

Section: Methylated Gata3 Is Able To Recruit Junb and Ets1 To The Il5mentioning

confidence: 99%

“…Conversely, the overexpression of Gata3 in Th1 cells switches their polarity to a Th2 phenotype (16). Gata3 forms functionally distinct complexes and controls the differentiation of naive CD4 T cells into Th2 cells by the induction of chromatin remodeling of the Th2 cytokine loci, facilitation of Th2 cell proliferation, and inhibition of Ifng (5,17,18). Gata3 also directly transactivates the Il5 gene via additional mechanisms that are not well understood (19 -21).…”

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confidence: 99%

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Methylation of Gata3 Protein at Arg-261 Regulates Transactivation of the Il5 Gene in T Helper 2 Cells

Hosokawa¹,

Kato²,

Tohyama³

et al. 2015

Journal of Biological Chemistry

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Background: Gata3 directly transactivates the Il5 gene. Results: The methylation-mimicking Gata3 mutant at Arg-261 had a selective defect in the induction of IL-5 production via recruitment of Hsp60 to prevent transactivation. Conclusion: Arginine methylation on Gata3 may play a critical role in the organization and function of the Gata3 transcriptional complex. Significance: A new regulatory mechanism of Gata3-mediated Il5 transactivation is revealed.

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Mifepristone Modulates the Polarization of Th1/Th2 by Inducing the Mature of Monocyte‐Derived Dendritic Cells

Li,

et al. 2023

Advanced Therapeutics

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As an anti‐implantation contraception medicine, mifepristone can alter the development of the endometrium. In contrast, little research has been performed to decipher the effect of mifepristone on Th1/Th2 immune homeostasis in the endometrium. CD14+ monocytes derived from healthy donors were cultured with interleukin‐4 (IL‐4) and granulocyte macrophage‐colony stimulating factor to induce monocyte‐derived dendritic cells (DCs), which were further incubated with mifepristone. Mifepristone incubation could induce up‐regulated CD83 and HLA‐DR staining on monocyte‐derived DCs. Functionally, mifepristone incubation could enhance the allostimulatory capacity of DCs to promote the proliferation of allogeneic T cells with up‐regulated Th1 cell proportion and down‐regulated Th2 cell proportion. On the other side, increased Th1 cytokines release (interferon‐γ, TNF‐α), inhibited Th2 cytokines release (IL‐10, IL‐4), promoted T‐Box transcription factor 21 transcription, and inhibited GATA binding protein 3 transcription were also identified. Mifepristone‐stimulated DCs could alter the Th1/Th2 transcription balance to favor Th1 skewing inflammatory environment.This article is protected by copyright. All rights reserved

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Functionally distinct Gata3/Chd4 complexes coordinately establish T helper 2 (Th2) cell identity

Cited by 77 publications

References 35 publications

Spi-B–Mediated Silencing of Claudin-2 Promotes Early Dissemination of Lung Cancer Cells from Primary Tumors

Spi-B–Mediated Silencing of Claudin-2 Promotes Early Dissemination of Lung Cancer Cells from Primary Tumors

Methylation of Gata3 Protein at Arg-261 Regulates Transactivation of the Il5 Gene in T Helper 2 Cells

Mifepristone Modulates the Polarization of Th1/Th2 by Inducing the Mature of Monocyte‐Derived Dendritic Cells

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