Mechanisms of Transcriptional Regulation by H3K4 Methyltransferases at CpG Islands

The genetic information of each cell is stored in the nucleus as DNA wrapped around histone proteins, a structure termed chromatin.

Apart from packaging DNA into the confined space of the nucleus, histone proteins serve as a template on which chemical modifications can be placed.

These modifications can determine whether the associated gene is actively being used to produce messenger RNA (mRNA) and subsequently its product. I am studying the four ‘writers’ of one such modification, tri-methylation of lysine 4 on histone H3 (H3K4me3).

These four enzymes, SET1A, SET1B, MLL1, and MLL2, have major roles in activating genes, but they seem to do so in a way that is separate and distinct from their roles as the writers of this modification.

To understand how these enzymes activate genes, I am using genetically engineered cells in which these enzymes can be rapidly degraded by treating the cells with a small molecule.

By removing these enzymes separately and in combination, I can analyse how these enzymes contribute to the overall levels of mRNA and H3K4me3 of the cell using sequencing techniques. The results of this project will be expected to increase our understanding of how genes are activated.