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Description

Histone-lysine N-methyltransferase SETDB1 (UniProt: O88974, also known as EC: 2.1.1.43, ERG-associated protein with SET domain, ESET, SET domain bifurcated 1) is encoded by the Setdb1 (also known as Eset, Kiaa0067) gene in human. SETDB1 is ubiquitously expressed, but a strong expression is observed in liver and testis. It is a histone methyltransferase that specifically trimethylates Histone 3 Lysine 9 (H3K9). H3K9 trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. It mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. SETDB1 is reported to inhibit adipogenesis. It has also been shown that H3K4/H3K9me3 bivalent chromatin signature keeps expression of Cebpa and Pparg genes very low. Depletion of SETDB1 can induce adipogenesis in mesenchymal stem cells and in preadipocytes. SETDB1 contains two Tudor domains (aa 257-320 and 347-403) and one MBD domain (aa 611-682). It also has a SET domain (aa 820-1282), a pre-SET (aa 744-817), and a post-SET domain (aa 1291-1307). The pre-SET, SET and post-SET domains are required for its methyltransferase activity. In the pre-SET domain, Cys residues bind 3 zinc ions that are arranged in a triangular cluster, some of these Cys residues contribute to the binding of two zinc ions within the cluster. (Ref.: Matsumura, Y., et al., (2015), Mol. Cell 60(4), 584- 596).