A chemiluminescence-based method for identification of histone lysine methyltransferase inhibitors

Synthesis of lysine methyltransferase inhibitors

Lysine methyltransferase which catalyze methylation of histone and non-histone proteins, play a crucial role in diverse biological processes and has emerged as a promising target for the development of various human diseases, including cancer, inflammation, and psychiatric disorders. However, inhibiting lysine methyltransferases selectively has presented many challenges to medicinal chemists. D...

Biological Functions of Dot1l, the Histone H3 Lysine 79 Methyltransferase

A Chemical Method for Labeling Lysine Methyltransferase Substrates

Several protein lysine methyltransferases (PKMTs) modify histones to regulate chromatin-dependent cellular processes, such as transcription, DNA replication and DNA damage repair. PKMTs are likely to have many additional substrates in addition to histones, but relatively few nonhistone substrates have been characterized, and the substrate specificity for many PKMTs has yet to be defined. Thus, ...

Histone lysine methyltransferase SETD8 promotes carcinogenesis by deregulating PCNA expression.

Although the physiologic significance of lysine methylation of histones is well known, whether lysine methylation plays a role in the regulation of nonhistone proteins has not yet been examined. The histone lysine methyltransferase SETD8 is overexpressed in various types of cancer and seems to play a crucial role in S-phase progression. Here, we show that SETD8 regulates the function of prolife...

Lysine methyltransferase SETD6 modifies histones and non-histone proteins

Although central to regulating the access to genetic information, most lysine methyltransferases remain poorly characterised relative to other family of enzymes. Herein, we report new substrates for the lysine methyltransferase SETD6. Based on the SETD6catalysed site on the histone variant H2AZ, we identified similar sequences in the canonical histones H2A, H3, and H4 that are modified by SETD6...