KAT8
KAT8 (lysine acetyltransferase 8, also known as MOF, hMOF and MYST1) is a MYST family histone acetyltransferase that acetylates histone H4, most notably at Lys-16. It also acetylates a range of non-histone proteins and acts in both the nucleus and mitochondria. Browse Assay Genie's current range of KAT8 research reagents below, or read on for the biology behind the target.
KAT8 catalyses histone H4 acetylation at Lys-5 and Lys-8 (H4K5ac and H4K8ac) or at Lys-16 (H4K16ac), depending on context. It is the catalytic component of the MSL histone acetyltransferase complex, which mediates most H4K16 acetylation, an epigenetic mark that prevents chromatin compaction. H4K16ac regulates processes such as oogenesis, embryonic stem cell pluripotency, haematopoiesis and glucose metabolism, and it is the only acetylation mark transmitted between generations. By maintaining homeostatic H4K16ac, the MSL complex supports chromosome stability and genome integrity. It also contributes to gene dosage, promoting up-regulation of X-chromosome genes and expression of the Tsix non-coding RNA.
As part of the NSL histone acetyltransferase complex, the KAT8 protein acetylates H4K5 and H4K8 at transcription start sites and promotes transcription initiation. The NSL complex also regulates gene expression in mitochondria: KAT8 associates with mitochondrial DNA and controls respiratory gene expression in an acetyltransferase-dependent manner. Beyond histones, KAT8 acetylates non-histone targets including ALKBH5, COX17, IRF3, KDM1A/LSD1, LMNA, PAX7 and p53 (at Lys-120). These activities link it to inhibition of antiviral immunity through IRF3, asymmetric division of muscle stem cells through PAX7, epithelial-to-mesenchymal transition through KDM1A, nuclear architecture through LMNA and mitochondrial integrity through COX17. It can also mediate protein propionylation.
The KAT8 gene encodes a member of the MYST family, also called the SAS/MOZ family. The protein has a MYST domain containing an acetyl-CoA-binding site, a histone-binding chromodomain and a C2HC-type zinc finger. Multiple transcript variants encoding different isoforms have been reported. HGNC lists the previous names MYST histone acetyltransferase 1 and K(lysine) acetyltransferase 8, and places KAT8 in the MSL and NSL histone acetyltransferase complex gene groups. Mouse and rat both have a Kat8 ortholog.
KAT8 drives H4K16 acetylation, a mark that prevents chromatin compaction, making it central to studies of histone modification and chromatin state.
The MSL and NSL complexes regulate X up-regulation, Tsix expression and transcription initiation at start sites through H4 acetylation.
KAT8 associates with mitochondrial DNA, controls respiratory gene expression and acetylates COX17 to promote mitochondrial integrity.
KAT8 acetylates PAX7 in muscle stem cell division and IRF3 to inhibit antiviral immunity, and it acts on p53 and KDM1A.
KAT8 is a histone acetyltransferase that acetylates histone H4 at Lys-16, or at Lys-5 and Lys-8 depending on its complex. It is the catalytic subunit of the MSL complex and acts within the NSL complex. It also acetylates non-histone proteins such as p53, IRF3 and LMNA.
KAT8 is also known as MOF, hMOF, MYST1 and FLJ14040. Earlier HGNC names were MYST histone acetyltransferase 1 and K(lysine) acetyltransferase 8. UniProt lists the protein as Histone acetyltransferase KAT8. Multiple transcript variants encoding different isoforms have been described.
Mouse and rat each have a Kat8 ortholog, and KAT8 belongs to the MYST (SAS/MOZ) family. Its roles in H4K16 acetylation and dosage compensation are described in the source annotation; check the datasheet of any product for its validated reactivity.
Other MYST family lysine acetyltransferases with related roles in histone acetylation and chromatin regulation.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q9H7Z6; product specifications from Assay Genie datasheets.