JARID1/KDM5 Histone Demethylase Antibody Sampler Kit#25497,Cell Signaling Technology (CST),25497

The methylation state of lysine residues in histone proteins is a major determinant for formation of active and inactive regions of the genome and is crucial for proper programming of the genome during development (1,2). Jumonji C (JmjC) domain-containing proteins represent the largest class of potential histone demethylase proteins (3). The JmjC domain can catalyze the demethylation of mono-, di-, and tri-methyl lysine residues via an oxidative reaction that requires iron and α-ketoglutarate (3). Based on homology, both humans and mice contain at least 30 such proteins, which can be divided into 7 separate families (3). The JARID (Jumonji/AT-rich interactive domain-containing protein) family contains four members: JARID1A (also RBP2 and RBBP2), JARID1B (also PLU-1), JARID1C (also SMCX), and JARID1D (also SMCY) (4). In addition to the JmJC domain, these proteins contain JmJN, BRIGHT, C5HC2 zinc-finger, and PHD domains, the latter of which binds to methylated histone H3 (Lys9) (4). All four JARID proteins demethylate di- and tri-methyl histone H3 Lys4; JARID1B also demethylates mono-methyl histone H3 Lys4 (5-7). JARID1A is a critical RB-interacting protein and is required for Polycomb-Repressive Complex 2 (PRC2)-mediated transcriptional repression during ES cell differentiation (8). A JARID1A-NUP98 gene fusion is associated with myeloid leukemia (9). JARID1B, which interacts with many proteins including c-Myc and HDAC4, may play a role in cell fate decisions by blocking terminal differentiation (10-12). JARID1B is overexpressed in many breast cancers and may act by repressing multiple tumor suppressor genes, includingBRCA1andHOXA5(13,14). JARID1C has been found in a complex with HDAC1, HDAC2, G9a, and REST, which binds to and represses REST target genes in non-neuronal cells (7). JARID1C mutations are associated with X-linked mental retardation and epilepsy (15,16). JARID1D is uniquely localized to the Y chromosome, and functions as a tumor suppressor by repressing genes associated with cell invasiveness (17). JARID1D is frequently mutated in metastatic prostate tumors, and low JARID1D levels are associated with poor prognosis in prostate cancer patients (17).Kubicek, S. et al. (2006)Ernst Schering Res Found Workshop, 1-27.Lin, W. and Dent, S.Y. (2006)Curr Opin Genet Dev16, 137-42.Klose, R.J. et al. (2006)Nat Rev Genet7, 715-27.Benevolenskaya, E.V. (2007)Biochem Cell Biol85, 435-43.Christensen, J. et al. (2007)Cell128, 1063-76.Yamane, K. et al. (2007)Mol Cell25, 801-12.Tahiliani, M. et al. (2007)Nature447, 601-5.Pasini, D. et al. (2008)Genes Dev22, 1345-55.van Zutven, L.J. et al. (2006)Genes Chromosomes Cancer45, 437-46.Secombe, J. et al. (2007)Genes Dev21, 537-51.Barrett, A. et al. (2007)Int J Cancer121, 265-75.Dey, B.K. et al. (2008)Mol Cell Biol28, 5312-27.Barrett, A. et al. (2002)Int J Cancer101, 581-8.Lu, P.J. et al. (1999)J Biol Chem274, 15633-45.Tzschach, A. et al. (2006)Hum Mutat27, 389.Jensen, L.R. et al. (2005)Am J Hum Genet76, 227-36.Li, N. et al. (2016)Cancer Res76, 831-43.