KDM6B

Official Full Name

lysine demethylase 6B

Organism

Homo sapiens

Gene ID

23135

Background

The protein encoded by this gene is a lysine-specific demethylase that specifically demethylates di- or tri-methylated lysine 27 of histone H3 (H3K27me2 or H3K27me3). H3K27 trimethylation is a repressive epigenetic mark controlling chromatin organization and gene silencing. This protein can also demethylate non-histone proteins such as retinoblastoma protein. Through its demethylation actvity this gene influences cellular differentiation and development, tumorigenesis, inflammatory diseases, and neurodegenerative diseases. This protein has two classical nuclear localization signals at its N-terminus. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Feb 2017]

Synonyms

JMJD3; NEDSST; NEDCFSA

Cat.No.	Product Name	Price
CSC-DC008055	Panoply™ Human KDM6B Knockdown Stable Cell Line	Inquiry
CSC-SC008055	Panoply™ Human KDM6B Over-expressing Stable Cell Line	Inquiry
CLKO-1033	KDM6B KO Cell Lysate-HEK293T	Inquiry

Cat.No.	Product Name	Price
AD08512Z	Human KDM6B adenoviral particles	Inquiry
LV16123L	human KDM6B (NM_001080424) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHH324279	shRNA set against Human KDM6B (NM_001080424.1)	Inquiry
SHH324283	shRNA set against Mouse KDM6B (NM_001017426.1)	Inquiry
SHH324287	shRNA set against Rat KDM6B (NM_001108829.1)	Inquiry
SHW009171	shRNA set against Danio rerio KDM6BB (NM_001030178)	Inquiry

Cat.No.	Product Name	Price
CDFH009747	Human KDM6B cDNA Clone(NM_001080424.1)	Inquiry
CDFR008397	Rat Kdm6b cDNA Clone(NM_001108829.1)	Inquiry
MiUTR1H-05070	KDM6B miRNA 3'UTR clone	Inquiry
MiUTR1M-06187	KDM6B miRNA 3'UTR clone	Inquiry
MiUTR1R-02736	KDM6B miRNA 3'UTR clone	Inquiry
SKO0556	KDM6B Validated sgRNA vector	Inquiry
CDCB170646	Danio rerio KDM6BB ORF Clone (NM_001030178)	Inquiry
CDCB191858	Rabbit KDM6B ORF clone (XM_008270772.1)	Inquiry
CDCL122393	Human Jmjd3 ORF clone (NM_001017426.1)	Inquiry
CDCL123661	Human KDM6B ORF clone (NM_001080424.1)	Inquiry
CDCR375452	Rat Kdm6b ORF Clone(NM_001108829.1)	Inquiry

Detailed Information

Recent Research

KDM6B, also known as Jmjd3, has been identified as an H3K27 demethylase that catalyzes the demethylation of H3K27me2/3. KDM6B is an inducible demethylase acting on H3K27me2,3, which represents an inhibitory epigenetic histone marker. Interestingly, expression of KDM6B can be activated by transcription factors that transduce signals triggered by inflammatory mediators and a variety of stress conditions. Induction of KDM6B is an important host defense response against environmental attack and cellular stress, as KDM6B stimulates a wide range of genes, including pro-inflammatory agents and factors that prevent cell proliferation. In addition, KDM6B regulates inflammatory responses through STAT6 (Signal transducers and activators of transcription), such as M2 polarization, and directs the typing of CD4+ T cells by T-bet factor. The p53 and INK4 box genes are major targets for the regulation of cellular senescence involved in KDM6B-induced senescence. KDM6B also prevents cancer formation by oncogene-induced senescence (OIS), as RAS and p53 signaling stimulate KDM6B function. Accordingly, KDM6B can produce developmental responses as well as induce cellular senescence. Therefore, KDM6B is an epigenetic regulator that is located in the relationship between inflammation and cellular senescence.

Recent studies in the molecular biology of KDM6B have shown that the expression of KDM6B can be induced by many inflammatory mediators as well as stress inducers such as metabolism, hypoxia and carcinogenic stress. Subsequently, KDM6B enhances transcription of inflammatory genes through a number of signaling pathways mediated by, for example, NF-κB, STAT, SMAD and T-bet transcription factors. KDM6B triggers transcription of the target gene by demethylating the inhibitory H3K27me3 epigenetic marker or mediating the interaction between chromatin modifiers, thereby activating gene transcription in a manner independent of demethylase.

KDM6B Figure 1. Schematic diagram depicting the regulatory network associated with KDM6B.

KDM6B also plays a key role in osteogenic differentiation by removing H3K27me3 from the promoter of osteogenic genes in human bone marrow stromal cells (BMSCs). A recent study showed that KDM6B plays a key role in epigenetic regulation of odontogenic differentiation of human dental pulp stem cells (DPSCs). In DPSCs, KDM6B knockdown studies resulted in decreased alkaline phosphatase activity and alizarin red staining, and decreased expression of marker genes, including osterix (OSX), osteocalcin (OCN) and osteopontin (OPN). KDM6B is involved in the control of calcium-induced differentiation, regulates osteoblast differentiation, promotes neuronal survival and differentiation, odontogenic differentiation of DPSC, and osteogenic differentiation of human BMSCs. Calcium-induced differentiation has been reported to result in increased binding of KDM6B and erasure of inhibitory markers such as H3K27me3. BMP4/7-mediated SMAD1/4 activation has been shown to induce KDM6B expression and trigger the osteogenic pathway. Mechanically, KDM6B is recruited to the bone morphogenetic protein 2 (BMP2) and HOX (homology gene) promoters and activates expression of genes associated with odontogenic differentiation. KDM6B removes the epigenetic marker H3K27me3 from the promoter of the osteogenic gene to promote osteogenic commitment. In addition, a recent study demonstrated the promotion of KDM6B to odontogenic differentiation.

KDM6B is known to play a key role in development, cancer, neurodegenerative diseases, aging and inflammatory diseases. Additionally, it has been reported that KDM6B can promote chondrocyte proliferation and hypertrophy during endochondral bone formation in KDM6B^−/− mice. Recent studies have shown that KDM6B is critical for cartilage development and homeostasis, and that abnormal changes in KDM6B expression in OA cartilage may provide a promising therapeutic target for OA therapy.

References:

Salminen A , et al. Histone demethylase Jumonji D3 (JMJD3/KDM6B) at the nexus of epigenetic regulation of inflammation and the aging process. Journal of Molecular Medicine, 2014, 92(10):1035-1043.
Yıldırım-Buharalıoğlu G, et al. Regulation of epigenetic modifiers, including KDM6B, by interferon-γ and interleukin-4 in human macrophages. Frontiers in immunology, 2017, 8: 92.
Yamamoto K , et al. Loss of histone demethylase KDM6B enhances aggressiveness of pancreatic cancer through downregulation of C/EBP. Carcinogenesis, 2014, 35(11):2404-2414.
Hoang M , et al. Alcohol-induced suppression of KDM6B dysregulates the mineralization potential in dental pulp stem cells. Stem Cell Research, 2016, 17(1):111-121.

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