KDM4D

Official Full Name

lysine demethylase 4D

Organism

Homo sapiens

Gene ID

55693

Background

Enables histone H3K9me2/H3K9me3 demethylase activity. Involved in inflammatory response. Acts upstream of or within several processes, including cellular response to ionizing radiation; double-strand break repair via homologous recombination; and positive regulation of double-strand break repair via nonhomologous end joining. Located in site of double-strand break. Biomarker of nephroblastoma. [provided by Alliance of Genome Resources, Feb 2025]

Synonyms

JMJD2D

Cat.No.	Product Name	Price
CSC-DC008048	Panoply™ Human KDM4D Knockdown Stable Cell Line	Inquiry
CSC-SC008048	Panoply™ Human KDM4D Over-expressing Stable Cell Line	Inquiry

Cat.No.	Product Name	Price
AD08506Z	Human KDM4D adenoviral particles	Inquiry
LV16115L	human KDM4D (NM_018039) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHH324223	shRNA set against Human KDM4D (NM_018039.2)	Inquiry
SHH324227	shRNA set against Mouse KDM4D (NM_173433.2)	Inquiry
SHH324231	shRNA set against Rat KDM4D (NM_001079712.1)	Inquiry

Cat.No.	Product Name	Price
CDFG001346	Human KDM4D cDNA Clone(NM_018039.2)	Inquiry
CDFL006517	Mouse Kdm4d cDNA Clone(NM_173433.2)	Inquiry
CDFR005033	Rat Kdm4d cDNA Clone(NM_001079712.1)	Inquiry
MiUTR1H-05069	KDM4D miRNA 3'UTR clone	Inquiry
MiUTR1M-06186	KDM4D miRNA 3'UTR clone	Inquiry
MiUTR1R-03536	KDM4D miRNA 3'UTR clone	Inquiry
CDCB188906	Rabbit KDM4D ORF clone (XM_002708442.2)	Inquiry
CDCL123631	Human KDM4D ORF clone (NM_018039.2)	Inquiry
CDCL123633	Mouse Kdm4d ORF clone (NM_173433.2)	Inquiry
CDCR372109	Rat Kdm4d ORF Clone(NM_001079712.1)	Inquiry
CDCS418819	Human KDM4D ORF Clone (BC122858)	Inquiry

Detailed Information

Recent Research

KDM4D is a lysine demethylase that removes tri- and di-methylated residues from H3K9 and is involved in transcriptional regulation and carcinogenesis. Human KDM4 (also known as JMJD2) family consists of four members (KDM4A–4D) that have an H3K9me3 demethylase activity. KDM4A, KDM4B and KDM4C also have the effect of demethylating trimethylated H3K36, while KDM4D is only specific for the demethylation of H3K9. In addition, KDM4D encodes shorter proteins than other KDM4 members and is more suitable for the production of recombinant proteins. KDM4D lysine demethylase is an RNA-binding protein that is localized to a KDM4D residue and mediates its interaction with RNA. KDM4D lysine deethylase is also a potential regulator of lysine 79-site trimethylation of H3. KDM4D, like other proteins in the KDM4 family, is also closely related to cancer.

A simple incubation of sheep fibroblast cells with recombinant human KDM4D protein could induce a remarkable reduction of H3K9. Human KDM4D has a function of demethylating H3K9me3 as well as H3K9me2 in sheep cells, confirming that this enzyme functions across mammalian species. Moreover, as KDM4D functions through an “active” demethylation pathway, it would induce a more rapid reduction of H3K9me3/me2 than methyltransferase inhibitors-mediated “passive” demethylation. More importantly, KDM4D can also demethylate H3K9me2 other than H3K9me3.

KDM4D is recruited to the DNA damage site in a manner dependent on parp1 to promote double-strand break repair in human cells. The c-terminal region of KDM4D mediates its rapid recruitment to DNA damage sites. This recruitment is independent of the DDR sensor ataxia telangiectasia mutated (ATM), but dependent on poly (ADP-ribose) polymerase 1 (PARP1), which ADP ribosylates KDM4D after damage.

KDM4D is required for efficient phosphorylation of a subset of ATM substrates. Deletion of KDM4D disrupts DNA-induced binding of ATM to chromatin and explains its effect on phosphorylation of ATM substrates. Consistent with the upstream action of DDR, KDM4D knockdown disrupts the formation of damage-induced recombinase Rad51 and tumor protein P53 binding proteins. Thus, in KDM4D deficient cells, homologous repair of DNA breaks and integrity of non-homologous end joining are impaired.

The presence of KDM4D drives fibrosis signaling by inducing TLR4 (Toll-like receptor 4). KDM4D is a histone demethylase that ACTS as an epigenetic regulator for the activation of hepatic stellate cells and regulates the occurrence of hepatic fibrosis by changing the methylation state of H3K9. KDM4D is a protein linked to H3K9 demethylation and HSC activation. Histone H3 methyltransferase and demethylase were up-regulated during HSC activation. KDM4D mainly leads to the decrease of H3K9me2 and H3K9me3 levels during the activation of HSC. Kdm4d gene silencing in HSCs leads to significant inhibition of TLR4 signaling pathway, and Kdm4d promotes TLR4 transcription through demethylation activity. The ligand involved in TLR4 receptor induces the activation of the receptor's intracellular signaling pathway through the recruitment adaptor MyD88, leading to the activation of the IB (B inhibitor) kinase complex and subsequent translocation of NF B p65(transcription factor protein family). Consistently, the expression level of TLR4 and the phosphorylated p65 as well as the fibrotic marker α-SMAb (Human smooth muscle actin) were markedly decreased in Kdm4d-deficient HSC, indicating that KDM4D is indeed indispensable for HSC activation and liver fibrogenesis in a TLR4/MyD88/NF-κB-dependent manner.

Histone demethylase KDM4D promotes gastrointestinal stromal tumor progression through HIF1β (aryl hydrocarbon re-eptor nuclear translocator) signaling. KDM4D plays a central role in GIST (Gastrointestinal stromal tumors) proliferation, migration and invasion both in vitro and in vivo. KDM4D is required for tumor angiogenesis by regulating the secretion of vascular endothelial growth factor (VEGFA). KDM4D directly interacts with the HIF1β gene promoter and regulatory activities, promoting tumor angiogenesis and progression (gastrointestinal stromal tumors) in vitro and in vivo. KDM4D transcription activates the promoter region of HIF1β (hypoxia-inducible factor-1) by demethylation of H3K9me3 and H3K36me3.

References:

Bur H , et al. Strong KDM4B and KDM4D Expression Associates with Radioresistance and Aggressive Phenotype in Classical Hodgkin Lymphoma. Anticancer research, 2016, 36(9):4677-4684.
Wu R , et al. H3K9me3 demethylase Kdm4d facilitates the formation of pre-initiative complex and regulates DNA replication. Nucleic Acids Research, 2017, 45(1):169-180.
Isohookana J , et al. KDM4D Predicts Recurrence in Exocrine Pancreatic Cells of Resection Margins from Patients with Pancreatic Adenocarcinoma. Anticancer research, 2018, 38(4):2295-2302.
Zhang Y , et al. Treatment of donor cells with recombinant KDM4D protein improves preimplantation development of cloned ovine embryos. Cytotechnology, 2018, 70(5):1-9.

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