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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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			Action	DRS
	SRR12186947.fastq.gz	Fastqsanger.gz
	SRR12186948.fastq.gz	Fastqsanger.gz
	SRR12186949.fastq.gz	Fastqsanger.gz
	SRR12186950.fastq.gz	Fastqsanger.gz
	SRR12186951.fastq.gz	Fastqsanger.gz

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Similar Datasets

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:Bone undergoes a constant and continuous remodeling process that is tightly regulated by the coordinated and sequential actions 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 identified KDM4B as an epigenetic regulator of osteoclast differentiation. Knockdown of KDM4B significantly blocked the formation of tartrate-resistant acid phosphatase-positive multinucleated cells. Mice with myeloid-specific conditional knockout of KDM4B showed an osteopetrotic phenotype due to osteoclast deficiency. Biochemical analysis revealed that KDM4B physically and functionally associates with CCAR1 and MED1 in a complex. Using genome-wide chromatin immunoprecipitation (ChIP)-sequencing, we revealed that the KDM4B-CCAR1-MED1 complex is localized to the promoters of several osteoclast-related genes upon receptor activator of NF-κB ligand stimulation. We demonstrated that the KDM4B-CCAR1-MED1 signaling axis induces changes in chromatin structure (euchromatinization) near the promoters of osteoclast-related genes through H3K9 demethylation, leading to NF-κB p65 recruitment via a direct interaction between KDM4B and p65. Finally, small molecule inhibition of KDM4B activity impeded bone loss in an ovariectomized mouse model. Taken together, our findings establish KDM4B as a critical regulator of osteoclastogenesis, providing a potential therapeutic target for osteoporosis.

| S-EPMC8144413 | biostudies-literature

Effect of CCAR1 depletion on androgen-dependent gene expression in LNCaP cells

Project description:Androgen receptor (AR) plays a critical role in prostate cancer onset and progression, and cell cycle and apoptosis regulator 1 (CCAR1) functions as an AR co-activator. We performed genome-wide gene expression analysis in control (shNS) and CCAR1-depleted (shCCAR1) LNCaP cells to assess the global effect of CCAR1 on the expression of androgen responsive genes. LNCaP cells expressing shNS or shCCAR1 were treated with ethanol or 10 nM DHT for 24 hr, and total RNA was isolated using the RNeasy mini kit (Qiagen). The integrity of RNA was analyzed using an Agilent 2100 Bioanalyzer. Two independent biological replicates were assayed for each sample. The microarrays were performed following the Affymetrix standard protocol.

2013-10-01 | E-GEOD-45033 | biostudies-arrayexpress

Effect of CCAR1 depletion on androgen-dependent gene expression in LNCaP cells

2013-10-01 | GSE45033 | 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

The Splicing Factor CCAR1 Regulates the Fanconi Anemia/BRCA Pathway

Project description:The twenty-three Fanconi Anemia proteins cooperate in a DNA repair pathway, called the FA/BRCA pathway, required for the monoubiquitination of FANCD2 and the excision of interstrand DNA crosslinks (ICLs). The CCAR1 (cell division cycle and apoptosis regulator 1) protein is also a regulator of ICL repair, though its possible function in the FA/BRCA pathway remains unknown. Here, we demonstrate that CCAR1 plays a unique upstream role in the FA/BRCA pathway and is required for FANCA protein expression and FANCD2 monoubiquitination. Interestingly, loss of CCAR1 results in retention of a poison exon in the FANCA transcript, thereby leading to reduced FANCA protein expression. A unique domain of CCAR1, the so-called EF-hand domain, binds to the spliceosome SF3B complex and is required for its mRNA splicing activity. Taken together, CCAR1 is a unique splicing factor, required for normal splicing of the FANCA mRNA and perhaps other mRNAs involved in various cellular pathways.

2024-08-21 | GSE242781 | GEO

ChIP-seq of Danio rerio wild type and kdm4b mutant embryos to investigate kdm4b signaling

Project description:chromatin immunoprecipitation sequencing (ChIP-seq) was performed to identify the targeted genes of kdm4b

2024-07-01 | E-MTAB-13114 | biostudies-arrayexpress

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

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

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

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