The histone demethylase Jmjd3 regulates zebrafish myeloid development by promoting spi1 expression

Yu, Shanhe; Zhu, Kunfu; Zhang, Fan; Wang, Juan; Yuan, Hao; Chen, Yi; Jin, Y.; Dong, Mei; Wang, Lei; Jia, Xiaoe; Gao, Lei; Dong, Zhiwei; Ren, Chunguang; Chen, Li-Ting; Huang, Qiu-Hua; Deng, Min; Zon, Leonard I.; Zhou, Yi; Zhu, Jiang; Xu, Pengfei; Liu, Tingxi

doi:10.1016/j.bbagrm.2017.12.009

Cited by 14 publications

(6 citation statements)

References 65 publications

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“…ChIP assays for NB4 cells and zebrafish embryos were performed essentially as previously described 29 , 32 with minor modifications. Briefly, cells were harvested and crosslinked with 1% formaldehyde for 10 min at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Tanshinone I, a new EZH2 inhibitor restricts normal and malignant hematopoiesis through upregulation of MMP9 and ABCG2

Huang¹,

Yu²,

Zhen³

et al. 2021

Theranostics

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Rationale: Tanshinone, a type of diterpenes derived from salvia miltiorrhiza , is a particularly promising herbal medicine compound for the treatment of cancers including acute myeloid leukemia (AML). However, the therapeutic function and the underlying mechanism of Tanshinone in AML are not clear, and the toxic effect of Tanshinone limits its clinical application. Methods: Our work utilizes human leukemia cell lines, zebrafish transgenics and xenograft models to study the cellular and molecular mechanisms of how Tanshinone affects normal and abnormal hematopoiesis. WISH, Sudan Black and O-Dianisidine Staining were used to determine the expression of hematopoietic genes on zebrafish embryos. RNA-seq analysis showed that differential expression genes and enrichment gene signature with Tan I treatment. The surface plasmon resonance (SPR) method was used with a BIAcore T200 (GE Healthcare) to measure the binding affinities of Tan I. In vitro methyltransferase assay was performed to verify Tan I inhibits the histone enzymatic activity of the PRC2 complex. ChIP-qPCR assay was used to determine the H3K27me3 level of EZH2 target genes. Results: We found that Tanshinone I (Tan I), one of the Tanshinones, can inhibit the proliferation of human leukemia cells in vitro and in the xenograft zebrafish model, as well as the normal and malignant definitive hematopoiesis in zebrafish. Mechanistic studies illustrate that Tan I regulates normal and malignant hematopoiesis through direct binding to EZH2, a well-known histone H3K27 methyltransferase, and inhibiting PRC2 enzymatic activity. Furthermore, we identified MMP9 and ABCG2 as two possible downstream genes of Tan I's effects on EZH2. Conclusions: Together, this study confirmed that Tan I is a novel EZH2 inhibitor and suggested MMP9 and ABCG2 as two potential therapeutic targets for myeloid malignant diseases.

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Section: Methodsmentioning

confidence: 99%

Tanshinone I, a new EZH2 inhibitor restricts normal and malignant hematopoiesis through upregulation of MMP9 and ABCG2

Huang¹,

Yu²,

Zhen³

et al. 2021

Theranostics

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“…Last, we also examined the role of jmjd3 in HSC commitment during zebrafish development with normal Vc. We injected morpholinos (MO) to knock down jmjd3 in flk1:mCherry/cmyb:GFP transgenic zebrafish (31). The flk1 ϩ cmyb ϩ emerging HSCs were remarkably reduced in jmjd3 morphants (Fig.…”

Section: Vitamin C and Jmjd3 Are Important For Hsc Emergence In Zebrafishmentioning

confidence: 99%

Vitamin C–dependent lysine demethylase 6 (KDM6)-mediated demethylation promotes a chromatin state that supports the endothelial-to-hematopoietic transition

Zhang

Huang

Zhu

et al. 2019

Journal of Biological Chemistry

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“…The ability of JMJD3 to demethylate H3K27me3 confers a role in activating transcription (11). JMJD3 acts in many biological processes such as neuronal differentiation (12), immunity (13), inflammation (14)(15)(16), hematopoiesis (17,18), osteogenesis (19)(20)(21)(22)(23) and embryonic development (24,25). Moreover, JMJD3 has a role in chromatin remodeling (26,27) and in cell reprogramming (28) independently of its demethylase activity.…”

mentioning

confidence: 99%

Effects of GSK-J4 on JMJD3 Histone Demethylase in Mouse Prostate Cancer Xenografts

Sánchez

Penault‐Llorca

Bignon

et al. 2022

Cancer Genomics Proteomics

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Background/Aim: Histone methylation status is required to control gene expression. H3K27me3 is an epigenetic tri-methylation modification to histone H3 controlled by the demethylase JMJD3. JMJD3 is dysregulated in a wide range of cancers and has been shown to control the expression of a specific growth-modulatory gene signature, making it an interesting candidate to better understand prostate tumor progression in vivo. This study aimed to identify the impact of JMJD3 inhibition by its inhibitor, GSK4, on prostate tumor growth in vivo. Materials and Methods: Prostate cancer cell lines were implanted into Balb/c nude male mice. The effects of the selective JMJD3 inhibitor GSK-J4 on tumor growth were analyzed by bioluminescence assays and H3K27me3-regulated changes in gene expression were analyzed by ChIP-qPCR and RT-qPCR. Results: JMJD3 inhibition contributed to an increase in tumor growth in androgen-independent (AR-) xenografts and a decrease in androgen-dependent (AR+). GSK-J4 treatment modulated H3K27me3 enrichment on the gene panel in DU-145-luc xenografts while it had little effect on PC3-luc and no effect onLNCaP-luc. Effects of JMJD3 inhibition affected the panel gene expression. Conclusion: JMJD3 has a differential effect in prostate tumor progression according to AR status. Our results suggest that JMJD3 is able to play a role independently of its demethylase function in androgenindependent prostate cancer. The effects of GSK-J4 on AR+ prostate xenografts led to a decrease in tumor growth.

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The histone demethylase Jmjd3 regulates zebrafish myeloid development by promoting spi1 expression

Cited by 14 publications

References 65 publications

Tanshinone I, a new EZH2 inhibitor restricts normal and malignant hematopoiesis through upregulation of MMP9 and ABCG2

Tanshinone I, a new EZH2 inhibitor restricts normal and malignant hematopoiesis through upregulation of MMP9 and ABCG2

Vitamin C–dependent lysine demethylase 6 (KDM6)-mediated demethylation promotes a chromatin state that supports the endothelial-to-hematopoietic transition

Effects of GSK-J4 on JMJD3 Histone Demethylase in Mouse Prostate Cancer Xenografts

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