SETD2 (E4W8Q) Rabbit mAb

SET domain-containing protein 2 (SETD2 or SET2), also known as lysine N-methyltransferase 3 A (KMT3A), huntingtin yeast partner B (HYBP), and huntingtin-interacting factor (HIF-1), is a ubiquitously expressed nuclear protein methyltransferase that is responsible for the majority of tri-methylation of histone H3 on lysine 36 (H3K36Me3) (1-3). SETD2-mediated H3K36Me3 is critical for proper regulation of transcription elongation, RNA splicing and DNA mismatch repair (1). SETD2 interacts with RNA polymerase II (RNAPII) that is hyper-phosphorylated on the C-terminal domain (CTD) of the largest subunit Rpb1 (2-4). Upon hyper-phosphorylation of the RNAPII CTD during activation of transcriptional elongation, SETD2 is recruited and facilitates tri-methylation of histone H3 lysine 36 in the body of transcriptionally active genes (2-4). H3K36Me3 then acts to recruit the transcription elongation factor FACT, which modulates nucleosome dynamics to facilitate transcription elongation and prevent cryptic transcriptional initiation (5). In addition, H3K36Me3 acts to recruit RNA-splicing proteins and regulate proper splicing of introns concurrent with transcriptional elongation (3, 6-9). In addition to regulating transcription, SETD2-dependent H3K36Me3 regulates DNA mismatch repair by recruiting MutSα (MSH2 and MSH6) to chromatin during G1 and early S phase (10). Loss of SETD2 results in an increase in microsatellite instability and elevated levels of spontaneous mutations (10). SETD2 is often mutated and/or inactivated in multiple types of cancer, including renal cell carcinoma, leukemia, melanoma and liver cancer (11-13). 1.Wagner, E.J. and Carpenter, P.B. (2012) Nat Rev Mol Cell Biol 13, 115-26. 2.Sun, X.J. et al. (2005) J Biol Chem 280, 35261-71. 3.Edmunds, J.W. et al. (2008) EMBO J 27, 406-20. 4.Yoh, S.M. et al. (2008) Genes Dev 22, 3422-34. 5.Carvalho, S. et al. (2013) Nucleic Acids Res 41, 2881-93. 6.Kolasinska-Zwierz, P. et al. (2009) Nat Genet 41, 376-81. 7.Luco, R.F. et al. (2010) Science 327, 996-1000. 8.Pradeepa, M.M. et al. (2012) PLoS Genet 8, e1002717. 9.de Almeida, S.F. et al. (2011) Nat Struct Mol Biol 18, 977-83. 10.Li, F. et al. (2013) Cell 153, 590-600. 11.Liao, L. et al. (2015) Cancer Genet 208, 206-14. 12.Chopra, M. and Bohlander, S.K. (2015) Cancer Genet 208, 192-205. 13.Kudithipudi, S. and Jeltsch, A. (2014) Biochim Biophys Acta 1846, 366-79.