ESET (D4M8R) XP^® Rabbit mAb #93212

The Erg-associated protein with SET domain (ESET), also known as SET-domain, bifurcated 1 (SETDB1) protein, is a member of a histone lysine methyltransferase family, each of which contains a conserved catalytic SET domain, originally identified in Drosophila Su[var]3-9, Enhancer of zeste, and Trithorax proteins (1). SETDB1 also contains tudor and methyl-CpG-binding domains, which may coordinate binding to methylated histones and methylated DNA, respectively (1). SETDB1 methylates histone H3 Lys9, creating a transcriptionally repressive mark that facilitates gene silencing (1-3). However, unlike SUV39H histone H3 Lys9 methyltransferases, which function mainly in heterochromatin regions, such as pericentric heterochromatin, SETDB1 functions mainly in euchromatic regions to repress gene promoters (3). SETDB1 interacts with a variety of proteins, including transcription factors (ERG), histone deacetylases (HDAC1/2), DNA methyltransferases (DNMT3A/B) and transcriptional co-repressors (mSin3A/B, MBD1, KAP-1, the ATFa-associated modulator mAM) (1-6). mAM forms a complex with SETDB1, stimulating its methyltransferase activity, specifically the conversion of di-methyl to tri-methyl histone H3 Lys9 (2). MBD1 recruits SETDB1 to the CAF-1 complex to facilitate methylation of histone H3 Lys9 during replication-coupled chromatin assembly in S phase (5). DNMT3A recruits SETDB1 to silenced promoters in cancer cells (7). SETDB1 may play a role in the pathogenesis of Huntington's disease, since levels of SETDB1 protein and tri-methyl histone H3 Lys9 are both increased in diseased brains (8).