Histone lysine demethylase KDM5B maintains chronic myeloid leukemia via multiple epigenetic actions

Xue, Sheng‐Li; Lam, Yuk Man; He, Zhikai; Zheng, Yan; Li, Lin; Zhang, Yonghong; Li, Chen; Mbadhi, Magdaleena Naemi; Zheng, Lanlan; Cheng, Zhongshan; Liu, Ying; Wang, Xuanbing; Li, Chan; Ng, Ray Kit; Zhang, Jingxuan

doi:10.1016/j.exphem.2020.01.006

Cited by 17 publications

(16 citation statements)

References 67 publications

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“…Similar to KDM5A, evidence suggests a pro-leukemic role for KDM5B in myeloid malignancies ( Figure 2 ). KDM5B is required for HSC self-renewal in mice [ 49 , 50 ] and is expressed in human CD34 + cells and in the CML cell line K562, as well as in several AML cell lines (Kasumi-1, KG-1, HEL, HL60, MonoMac-60) ( Table 1 ) [ 46 ]. Knockdown of KDM5B in K562 cells has shown to reduce colony-forming potential [ 46 ].…”

Section: Resultsmentioning

confidence: 99%

“…KDM5B is required for HSC self-renewal in mice [ 49 , 50 ] and is expressed in human CD34 + cells and in the CML cell line K562, as well as in several AML cell lines (Kasumi-1, KG-1, HEL, HL60, MonoMac-60) ( Table 1 ) [ 46 ]. Knockdown of KDM5B in K562 cells has shown to reduce colony-forming potential [ 46 ]. Recent expression data from CML patients show that during chronic phase KDM5B level are not changed compared to healthy controls, but significantly increase in CML-BP [ 116 ].…”

Section: Resultsmentioning

confidence: 99%

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The Cross Marks the Spot: The Emerging Role of JmjC Domain-Containing Proteins in Myeloid Malignancies

2021

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Histone methylation tightly regulates chromatin accessibility, transcription, proliferation, and cell differentiation, and its perturbation contributes to oncogenic reprogramming of cells. In particular, many myeloid malignancies show evidence of epigenetic dysregulation. Jumonji C (JmjC) domain-containing proteins comprise a large and diverse group of histone demethylases (KDMs), which remove methyl groups from lysines in histone tails and other proteins. Cumulating evidence suggests an emerging role for these demethylases in myeloid malignancies, rendering them attractive targets for drug interventions. In this review, we summarize the known functions of Jumonji C (JmjC) domain-containing proteins in myeloid malignancies. We highlight challenges in understanding the context-dependent mechanisms of these proteins and explore potential future pharmacological targeting.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

The Cross Marks the Spot: The Emerging Role of JmjC Domain-Containing Proteins in Myeloid Malignancies

2021

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“…However, these studies mainly focus on embryonic development and tumor, with little involvement in the induction and differentiation regulation of adult stem cells. During the differentiation of stem cells into cardiomyoid cells, histone modi cation enzymes cluster in the transcription regulatory region of cardiac genes, forming histone modi cation enzyme-transcription factor complex to regulate gene expression and cell differentiation [31]. In this study, different groups of BMSCs were induced into myocardium, and it was found that the expression of HCN4, a key gene of myocardial differentiation, was increased in the KDM5B overexpression group, while signi cantly decreased in the KDM5B silencing group, which led to the change of cell membrane surface current density after differentiation, changing the physiological function of the differentiated cells.…”

Section: Discussionmentioning

confidence: 99%

Histone demethylase KDM5B catalyzed H3K4me3 demethylation to promote differentiation of bone marrow mesenchymal stem cells into cardiomyocytes

Wang

Zhong

2022

Preprint

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BACKGROUND: Studies have shown that histone H3 methylation is involved in regulating the differentiation of Bone Marrow Mesenchymal Stem Cells (BMSCs). KDM5B can specifically reduce the level of histone 3 lysine 4 trimethylation (H3K4me3), thereby activating the expression of related genes and participating in biological processes such as cell differentiation, embryonic development and tumor formation. Whether KDM5B is involved in the regulation of BMSCs differentiation into cardiomyocytes through the above manner has not been reported.OBJECTIVE: To investigate the effect of KDM5B on the induction and differentiation of swine BMSCs into myocardial cells in vitro.METHODS: Swine bone marrow BMSCs were isolated and cultured, and the overexpression, interference expression and blank vector of KMD5B were constructed and transfected by lentivirus. BMSCs was induced to differentiate into cardiomyocytes by 5-azacytidine (5-AZA) in vitro, and the differentiation efficiency was compared by immunofluorescence, RT-PCR, Western Blot and whole-cell patch clamp detection.RESULT: Compared with the control group, the expression levels of histone H3K4me3 and pluripotency gene Nanog in KDM5B overexpression group were significantly decreased, while the expression level of key myocardial gene HCN4 and myocardial marker gene α-Actin and cTNT were significantly increased, and the Na+ current density on the surface of differentiated myocardial cell membrane was significantly increased. Meanwhile, the corresponding results of the KDM5B silent expression group were just opposite. CONCLUSIONS: It indicated that enhanced KDM5B expression could promote the differentiation of BMSCs into cardiomyocytes and improve the differentiation efficiency by controlling H3K4 methylation levels.

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“…Furthermore, studies found that H3K4me3 co-localizes with the KDM5B demethylase enzyme at promoter regions of active genes ( Kidder et al, 2014 ; Xue et al, 2020 ). Inhibition of KDM5B resulted in widespread H3K4 methylation into gene bodies, leading to defects in gene expression and impairment in the self-renewal and differentiation of embryonic cells ( Kidder et al, 2014 ).…”

Section: Histone Modification In Muscle Development and Regenerationmentioning

confidence: 99%

“…Inhibition of KDM5B resulted in widespread H3K4 methylation into gene bodies, leading to defects in gene expression and impairment in the self-renewal and differentiation of embryonic cells ( Kidder et al, 2014 ). Thus, it is proposed that KDM5B has significance in localising H3K4 methylation at the promoter and enhancer regions of relevant genes ( Kidder et al, 2014 ; Xue et al, 2020 ). Whether similar regulatory mechanisms of KDM5B in muscle-regulated genes also exist is yet to be explored.…”

Section: Histone Modification In Muscle Development and Regenerationmentioning

confidence: 99%

Histone Lysine Methylation and Long Non-Coding RNA: The New Target Players in Skeletal Muscle Cell Regeneration

Mbadhi

Tang

Zhang

2021

Front. Cell Dev. Biol.

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Satellite stem cell availability and high regenerative capacity have made them an ideal therapeutic approach for muscular dystrophies and neuromuscular diseases. Adult satellite stem cells remain in a quiescent state and become activated upon muscular injury. A series of molecular mechanisms succeed under the control of epigenetic regulation and various myogenic regulatory transcription factors myogenic regulatory factors, leading to their differentiation into skeletal muscles. The regulation of MRFs via various epigenetic factors, including DNA methylation, histone modification, and non-coding RNA, determine the fate of myogenesis. Furthermore, the development of histone deacetylation inhibitors (HDACi) has shown promising benefits in their use in clinical trials of muscular diseases. However, the complete application of using satellite stem cells in the clinic is still not achieved. While therapeutic advancements in the use of HDACi in clinical trials have emerged, histone methylation modulations and the long non-coding RNA (lncRNA) are still under study. A comprehensive understanding of these other significant epigenetic modulations is still incomplete. This review aims to discuss some of the current studies on these two significant epigenetic modulations, histone methylation and lncRNA, as potential epigenetic targets in skeletal muscle regeneration. Understanding the mechanisms that initiate myoblast differentiation from its proliferative state to generate new muscle fibres will provide valuable information to advance the field of regenerative medicine and stem cell transplant.

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Histone lysine demethylase KDM5B maintains chronic myeloid leukemia via multiple epigenetic actions

Cited by 17 publications

References 67 publications

The Cross Marks the Spot: The Emerging Role of JmjC Domain-Containing Proteins in Myeloid Malignancies

The Cross Marks the Spot: The Emerging Role of JmjC Domain-Containing Proteins in Myeloid Malignancies

Histone demethylase KDM5B catalyzed H3K4me3 demethylation to promote differentiation of bone marrow mesenchymal stem cells into cardiomyocytes

Histone Lysine Methylation and Long Non-Coding RNA: The New Target Players in Skeletal Muscle Cell Regeneration

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