ESET/KMT1E/SETDB1 [G4]

ERG-associated protein with SET domain (ESET), also designated Histone H3-K9 methyltransferase 4 or SET domain bifurcated 1, is a nuclear protein belonging to the histone-lysine methyltransferase family and to the Suvar3-9 subfamily. It is a highly conserved protein of 150 amino acids that has been implicated in chromatin structure modulation. ESET is excluded from cell nucleoli and areas of condensed chromatin and can associate with the nonpericentromeric regions of chromatin. The gene encoding for this protein, SETDB1, maps to chromosome 1q21.3. ESET is a histone methyltransferase, methylating Lys 9 of Histone H3 and mutations within the SETDB1 gene abolishes its methyltransferase activity. This methylation acts as a tag for epigenetic transcriptional repression by rounding up HP1 proteins to methylated histones. ESET is widely expressed with highest levels found in testis. ESET may play a role in the pathogenesis of Huntington’s disease, since levels of ESET protein and tri-methyl histone H3 Lys9 are both increased in diseased brains.