Histone acetyltransferase KAT7 (KAT7)

Histone acetyltransferase KAT7, also known as HBO1 or MYST2, is a catalytic enzyme belonging to the MYST family that plays a pivotal role in epigenetic regulation and DNA replication. It primarily functions by acetylating histone H3 at lysine 14 (H3K14) and various lysine residues on histone H4, thereby modulating chromatin structure to facilitate gene transcription (UniProt: O95251). Crucially, KAT7 is essential for the initiation of DNA replication, as it interacts with the Origin Recognition Complex (ORC) to promote the loading of the MCM2-7 helicase onto chromatin (PubMed: 10835352). In oncology, KAT7 is recognized as a significant driver in certain malignancies, particularly acute myeloid leukemia (AML), where it maintains the expression of HOXA genes necessary for leukemic stem cell survival (Nature: 10.1038/s41586-020-1991-7). Therapeutic strategies focus on small-molecule inhibitors like WM-1119 that block the KAT7 acetyltransferase domain, leading to cell cycle arrest and differentiation of cancer cells (PubMed: 32051583). While promising, the target's fundamental role in cellular proliferation necessitates careful evaluation of potential toxicities related to DNA replication and normal hematopoiesis.

Other names

HBO1MYST2Histone acetyltransferase binding to ORC1MYST histone acetyltransferase 2HBOALysine acetyltransferase 7

Inhibition of the acetyltransferase activity of KAT7, specifically reducing H3K14 acetylation, which leads to the transcriptional repression of oncogenic genes and induction of cellular senescence or differentiation.