SAN DIEGO -- FBXL11 (KDM2A) and FBXL10 (KDM2B) are F-box and Jumonji domain-containing enzymes that specifically demethylate mono- and di-methylated lysine 36 of histone H3 (H3K36) in a Fe(II) and α-ketoglutarate (αKG)-dependent manner. Unlike most methyllysine histone modifications, methylation of H3K36 is associated with active chromatin and gene transcription. FBXL10 was also reported to exhibit H3K4 demethylase activity, another histone mark associated with active gene expression. The role of FBXL10 is controversial, as it contributes to a number of seemingly contradictory physiological functions, including apoptosis, senescence, and tumorigenesis, where dysregulation of FBXL10 expression has been linked to various aggressive brain tumors. FBXL11 is required to maintain the heterochromatic state and sustain genomic stability during mitosis. In addition to H3K36 demethylation, FBXL11 can demethylate the p65 subunit of NF-κB, suppressing NF-κB-dependent cancer growth.
SETDB1, also known as ESET or KMT1E, is a histone methyltransferase that specifically methylates lysine 9 on histone H3 (H3K9), the highly studied epigenetic modification associated with transcriptional repression. SETDB1 activity is required to maintain embryonic stem cells and neurons in an undifferentiated state. The SETDB1 gene is amplified in melanoma, and SETDB1 hypermethylation promotes melanoma formation and growth, making SETDB1 inhibition a promising therapeutic target for melanoma and other human cancers. Hypermethylation of H3K9 is also linked to Huntington Disease; downregulation of SETDB1 activity in transgenic mice ameliorated the behavioral and neuropathological phenotype and extended survival by an astounding 40%*.
Because of the critical importance of histone methylation in cell proliferation, differentiation, senescence, and tumorigenesis, researchers are actively seeking small molecule regulators of histone methylation as targets for drug discovery. BPS is the first company to offer assay kits to screen for modulators of FBXL10, FBXL11, and SETDB1. The assays are simple, sensitive, homogeneous, non-radioactive, and suitable for high throughput applications.
In addition to offering these unique assay kits, BPS offers methyltransferase and demethylase screening/profiling services, as well as the individual recombinant proteins, substrates, and H3K9 and H3K36 methylation-specific antibodies. The new kits complement the largest selection of commercially available recombinant methyltransferases and demethylases for epigenetic research. Additional tools and services for histone methylation/demethylation are planned for release in the coming months, as BPS continues to assist life science researchers at the forefront of cancer drug discovery.
To learn more about BPS’s demethylase and methyltransferase products, please visit http://bpsbioscience.com/demethylase or http://bpsbioscience.com/methyltransferase. For additional information on BPS’s epigenetic screening services, please visit http://bpsbioscience.com/biological-services.
*Ryu, H., et al. Proc Natl Acad Sci U S A. (http://www.ncbi.nlm.nih.gov/pubmed/17142323) 2006 Dec 12;103(50):19176-81.
About BPS Bioscience, Inc.
Headquartered in San Diego, California, BPS Bioscience, Inc. is the leading manufacturer of epigenetic enzymes and assay kits for life science research, including HDACs, histone demethylases, DNA and histone methyltransferases, bromodomains, PARPs, acetyltransferases, methyl lysine readers, and more. BPS also offers compound screening and profiling services and cell based assays for epigenetic drug discovery. BPS has provided products and services to pharmaceutical companies and academic institutes in over 45 countries worldwide, and it continues to expand its portfolio of innovative drug discovery products. By being at the forefront of technology development, BPS focuses on providing quality life science products and services in a timely manner that will help our customers to accelerate drug discovery and development for treatment of human diseases. Visit BPS’s website for more information: http://www.bpsbioscience.com.
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