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Series GSE154125 Query DataSets for GSE154125
Status Public on Jun 30, 2021
Title KDM4B-CCAR1-Mediator axis is a critical regulator of osteoclast differentiation and bone homeostasis
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary 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.
 
Overall design ChIP-sequencing of KDM4B, CCAR1, MED1 and p65 in BMM cells with RANKL treatment. High-throughput sequencing was performed as single read 75bp sequencing using HigSeq 2500.
 
Contributor(s) Kim K
Citation(s) 34031372
Submission date Jul 09, 2020
Last update date Sep 30, 2021
Contact name Kyunghwan Kim
E-mail(s) kyungkim@chungbuk.ac.kr
Organization name Chungbuk National University
Street address Rm #202a, Bldg. S1-5, 1 chungdae-ro
City Cheongju
ZIP/Postal code 28644
Country South Korea
 
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (5)
GSM4664306 input DNA
GSM4664307 KDM4B_ChIPseq
GSM4664308 CCAR1_ChIPseq
Relations
BioProject PRJNA645166
SRA SRP271145

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE154125_RAW.tar 900.5 Mb (http)(custom) TAR (of BIGWIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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