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KDM4B-CCAR1-Mediator axis is a critical regulator of osteoclast differentiation and bone homeostasis

ABSTRACT: KDM4B-CCAR1-Mediator axis is a critical regulator of osteoclast differentiation and bone homeostasis

PROVIDER: PRJNA645166 | ENA |

REPOSITORIES: ENA

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KDM4B-CCAR1-Mediator axis is a critical regulator of osteoclast differentiation and bone homeostasis

Project description:Bone undergoes a constant and continuous remodeling process which is tightly regulated by the coordinated and the sequential action of bone-resorbing osteoclasts and bone-forming osteoblasts. Recent studies have shown that histone demethylases are implicated in osteoblastogenesis. However, little is known about the role of histone demethylases in osteoclast formation. Here, we identify KDM4B as an epigenetic regulator of osteoclast differentiation.Our biochemical analysis revealed that KDM4B physically and functionally associates with CCAR1 and Med complex. Using chromatin immunoprecipitation (ChIP) with sequencing, we revealed that KDM4B-CCAR1-Med1 is localized at the promoters of several osteoclast-related genes after RANKL stimulation. We demonstrated that KDM4B-CCAR1-MED1 axis is required for p65 localization at the promoters of osteoclast-related genes through a direct interaction between KDM4B and p65 and changes in chromatin structures (euchromatinization). Finally, small-molecular inhibition of KDM4B impedes bone loss in the ovariectomized mouse model. Taken together, our findings establish KDM4B as a critical regulator of osteoclastogenesis, providing a potential therapeutic target of osteoporosis.

2021-06-30 | GSE154125 | GEO

The KDM4B-CCAR1-MED1 axis is a critical regulator of osteoclast differentiation and bone homeostasis.

Project description: Not available

| S-EPMC8144413 | biostudies-literature

Expression analysis of blastocysts in Kdm4b-PEs

Project description:To identify the genes that are controled by H3K9me3 modification in PEs, we conducted transcriptome analysis using Egfp-, Kdm4b-PEs, and IVF embryos at blastocyst stages. Kdm4b or Egfp mRNA injected oocytes were parthenogenetically activated. IVF embryos were generated according to standard protcol. All embryos were cultured in KSOM medium for 120 hours after activation or sperm insemination. Five blastocysts per one biological replicate were pooled and analyzed.

2014-11-15 | E-GEOD-53662 | biostudies-arrayexpress

KDM4B- and KDM6B-regulated genes in human mesenchymal stem cell osteogenic differentiation

Project description:To investigate how histone demethylases KDM4B and KDM6B may be involved in osteogenic commitment of mesenchymal stem cells (MSCs), we performed gene expression profiling and comparison on control, KDM4B- and KDM6B-knockdown MSCs at different stages of osteogenic differentiation. Human MSCs infected with scramble shRNAs, shRNAs against KDM4B or KDM6B are treated with BMP4/7 for 0, 4 and 24hrs. Total RNA were extracted from these 9 samples.

2012-07-31 | E-GEOD-36970 | biostudies-arrayexpress

The Blimp1-Bcl6 axis is critical to regulate osteoclast differentiation and bone homeostasis.

Project description: Not available

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Transcriptomic analysis of KDM4B-mediated genes in AGS cells

Project description:KDM4B, an important epigenetic regulator of cell proliferation, metastasis and genome stability, is often overexpressed in gastric cancer. Notably, elevated expression of KDM4B is associated with a poor clinical outcome. A global transcriptomic analysis between KDM4B control and KDM4B-knockdown AGS cells without or with Helicobacter pylori challenge reveals differentially expressed genes involved in response to virus, multi-organism process, and response to stimulus, suggesting KDM4B as an inducible epigenetic factor under H. pylori challenge.

2019-02-05 | GSE107703 | GEO

Histone demethylase KDM4B promotes DNA damage by activating long interspersed nuclear element-1

Project description:We assess whole-genome H3K9me3 distribution in cancer cells and find that H3K9me3 is largely enriched in long interspersed nuclear element-1 (LINE-1). A significant proportion of KDM4B-dependent H3K9me3 was located in evolutionarily young LINE-1 elements, which likely retain retrotransposition activity. Ectopic expression of KDM4B promoted LINE-1 expression, while depletion of KDM4B reduced it. Furthermore, KDM4B overexpression enhanced LINE-1 retrotransposition efficacy, copy number, and associated DNA damage, presumably via the histone demethylase activity of KDM4B. Breast cancer cell lines expressing high levels of KDM4B also exhibited increased LINE-1 expression and copy number compared with other cell lines. Pharmacological inhibition of KDM4B significantly reduced LINE-1 expression and DNA damage in breast cancer cells with excessive KDM4B. Our study not only identifies KDM4B as a novel regulator of LINE-1, but it also suggests an unexpected oncogenic role for KDM4B overexpression in tumorigenesis, providing clues for the development of new cancer prevention strategies and therapies.

2018-10-24 | GSE121642 | GEO

KDM4B epigenetically protects against obesity and metabolic dysfunction [gene expression]

Project description:KDM4B (lysine demethylase 4B) in adipose tissues plays a critical role in energy balance, oxidation, lipolysis and thermogenesis. Loss of KDM4B in mice resulted in obesity associated with reduced energy expenditure and impaired adaptive thermogenesis. Mechanistically, we determined that KDM4B directly controls the expression of multiple metabolic genes.

2019-05-22 | GSE102289 | GEO

Transcriptomic analysis of KDM4B-mediated gene in C4-2B prostate cancer cells

Project description:Histone lysine demethylase KDM4B is often overexpressed in prostate cancer and links to poor survival outcome. Recent evidence suggests that KDM4B serves as a potential therapeutic target. The global transcriptomic analysis between control and KDM4B-knockdown C4-2B cells reveals the metabolic genes involved in Warburg effect are downregulated after knocking down the expression of KDM4B, indicating its role in tumor growth.

2023-03-24 | GSE147481 | GEO

KDM4B regulates alternative splicing in castration resistant prostate cancer

Project description:We studied the alternative splicing function of KDM4B and found that KDM4B can act as a bona fide trans-acting splicing factor that binds RNA and signal-responsive scaffold protein that binds spliceosome.

2020-04-01 | GSE130620 | GEO

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