SET1/MLL family of proteins: functions beyond histone methylation

ABSTRACT

The SET1 family of enzymes are well known for their involvement in the histone 3 lysine 4 (H3K4) methylation, a conserved trait of euchromatin associated with transcriptional activation. These methyltransferases are distinct, and involved in various biological functions in the cell. Impairment in the function of SET1 family members leads to a number of abnormalities such as skeletal and neurological defects, leukaemogenesis and even lethality. Tremendous progress has been made in understanding the unique biological roles and the mechanism of SET1 enzymes in context with H3K4 methylation/canonical functions. However, in recent years, several studies have indicated the novel role of SET1 family proteins, other than H3K4 methylation, which are equally important for cellular functions. In this review, we focus on these non-canonical function of SET1 family members.

KEYWORDS:

• MLL
• SETD1A
• H3K4 histone methyltransferase
• non-canonical functions
• cell cycle
• non-histone protein substrates

Acknowledgements

We thank A. Bakshi and R. Joshi for their critical reading, and G.B. Srinivas for editing of the manuscript. JS is recipient of Research Associateship from Department of Biotechnology (DBT), India.

Author contributions

S.T. conceived and designed the content of the review. J.S. and J.G. prepared the figures and the tables. J.S., J.G and S.T. wrote the manuscript.

Disclosure statement

The authors declare that they have no conflict of interest.

Additional information

Funding

This work was supported in part by the DBT/Wellcome Trust India Alliance Senior Fellowship to S.T.[IA/S/18/2/503981], and grants by Department of Biotechnology (DBT) [BT/PR13351/BRB/10/1403/2015] and Department of Science and Technology [EMR/2016/000406], Government of India to S.T.