KDM5B

Official Full Name

lysine demethylase 5B

Organism

Homo sapiens

GeneID

10765

Background

This gene encodes a lysine-specific histone demethylase that belongs to the jumonji/ARID domain-containing family of histone demethylases. The encoded protein is capable of demethylating tri-, di- and monomethylated lysine 4 of histone H3. This protein plays a role in the transcriptional repression or certain tumor suppressor genes and is upregulated in certain cancer cells. This protein may also play a role in genome stability and DNA repair. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]

Synonyms

CT31; PLU1; PUT1; MRT65; PLU-1; JARID1B; PPP1R98; RBP2-H1; RBBP2H1A;

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Detailed Information

Recent Research

Lysine-specific histone demethylase 5B (KDM5B, also known as JARID1B or PLU-1) catalyzes the demethylation of trimethylated H3K4 (H3K4me3 and H3K4me2) to a monomethylated form (H3K4me1). KDM5B is a jmjc domain containing histone demethylase and belongs to the KDM5 family. KDM5B was first identified in 1999 when Lu was found to be overexpressed in human breast cancer cell lines and primary breast cancer. Mammalian KDM5B shows a restricted expression pattern in normal adult tissues and is mainly present in the testis and brain. However, KDM5B levels have been found to be upregulated in a variety of human cancers, such as bladder cancer, lung cancer, colorectal cancer, prostate cancer, gastric cancer, glioma, ovarian cancer, and malignant melanoma.

The expression level of KDM5B is highly dependent on the type of cancer cell. KDM5B is down-regulated in ER- breast cancer cells, including mda-mb 231 triple negative breast cancer cells, consistent with previous findings that it is up-regulated in ER+ breast cancer cells such as MCF7 (human breast cancer cells). Two PHD fingers of KDM5B, PHD1 and PHD3 are associated with histone tails. PHD1 refers to specific binding to H3K4me0, and PHD3 is selective for H3K4me3. Thus, KDM5B demethylase not only eliminates the H3K4me3/2/1 label, but also produces unmodified H3K4me0, which also reads the target label and its own catalytically active product through different PHD fingers. The combination of two "readers" that recognize unique epigenetic markers may have a significant effect on KDM5B activity. Binding of PHD1 to H3K4me0 provides an anchoring mechanism for KDM5B to sense H3K4me3 via PHD3 and slide along the H3K4me3-rich promoter to demethylate nearby methylated H3K4 and further diffuse chromatin inactivation.

KDM5B Figure 1: A model for KDM5B anchoring at chromatin and spreading the transcriptionally inactive state.

KDM5B and NuRD (Nuclear underweight structure and histone deacetylase) also can cooperate in transcriptional repression. The NuRD complex contains two catalytic subunits, the deacetylase HDAC1 (Histone Deacetylase 1 antibody) and the CHD4 (chromodomain helicase DNA binding protein) ATPase, and two subunits are essential for gene expression regulation and chromatin remodeling. A cooperative action of the three catalytic proteins, KDM5B, HDAC1 and CHD4, links H3K4-demethylation, lysine deacetylation and ATPase-mediated chromatin remodeling, providing a powerful mechanism for a rapid shut off of actively transcribed genes. Histone-binding activities of two PHD fingers of CHD4 and the WD40 domain of RBBP7/4 (Homo sapiens retinoblastoma binding protein), as well as DNA binding by the ARID domain of KDM5B and two chromodomains of CHD4 may fine tune the affinity and specificity of this gene repressive machinery.

KDM5B is significantly overexpressed in gastric cancer, suggesting that KDM5B is a candidate oncogene for gastric cancer. Overexpression of KDM5B in vitro significantly enhanced the proliferation, migration and invasion of gastric cancer cells, while knockdown of KDM5B inhibited cell growth and migration. Some experiments have also demonstrated that KDM5B significantly promotes tumorigenesis and metastasis to the liver in vivo. These data further support the role of KDM5B in oncogenes in gastric cancer.

Studies have also shown that KDM5B colocalizes with the H3K4 methylation marker on the enhancer and promoter of the activating gene, accumulating H3K4 methylation near these regulatory regions by preventing their spread to the genome and enhancer coast, and for ES (embryonic stem) enhancer activity is critical. In addition, KDM5B regulates H3K4 methylation of the bivalent (H3K4me3 / H3K27me3) developmental genes during differentiation. KDM5B and LSD1 together regulate H3K4 methylation in the active promoter region of ES cells, but their functions remain different in the bivalent developmental genes and gene regions. Overall, KDM5B regulates ES cell pluripotency by modulating chromatin in a way that is conducive for differentiation.

References:

Li X , et al. Histone demethylase KDM5B is a key regulator of genome stability. Proceedings of the National Academy of Sciences, 2014, 111(19):7096-7101.
Xie L , et al. KDM5B regulates embryonic stem cell self-renewal and represses cryptic intragenic transcription. EMBO JOURNAL, 2011, 30(8):1473-1484.
Wang Z , et al. KDM5B is overexpressed in gastric cancer and is required for gastric cancer cell proliferation and metastasis. American Journal of Cancer Research, 2015, 5(1):87-100.
Bamodu O A , et al. Aberrant KDM5B expression promotes aggressive breast cancer through MALAT1 overexpression and downregulation of hsa-miR-448. BMC Cancer, 2016, 16(1):160.

Quick Inquiry

Interested in learning more?

Contact us today for a free consultation with the scientific team and discover how Creative Biogene can be a valuable resource and partner for your organization.

Request a quote today!

Inquiry