Research Overview

Fig 1. hMOF is responsible for bulk H4K16Ac

Fig 2. hMOF expression and H4K16 acetylation in normal tissue and cancers

Epigenetic mechanisms act above the level of DNA, controlling gene expression patterns and hence dictating the proper development of an organism. Various epigenetic mechanisms are now recognized and include; modification of the DNA, modifications of histone proteins and incorporation of histone variants.

To better understand epigenetic mechanisms, in particular, the role of histone acetylation in the regulation of gene expression, we are studying the human MOF complex in cultured human cells and tumor cell lines. hMOF is an enzyme responsible for the acetylation of histone H4 at lysine 16 (fig 1). In the fruit fly this H4K16 acetylation correlates with a two-fold upregulation of transcription required for dosage compensation.

The purification of MOF-interacting proteins from the fruitfly and human cells revealed a number of conserved interacting proteins, suggesting that the function of these complexes is maintained through evolution. Recently, it was found that loss of hMOF and also reduction in H4K16 acetylation levels are frequent occurrences in various human cancers (fig 2). Thus, studying hMOF and H4K16 acetylation allows us to investigate the role of this particular modification in normal development and its involvement in cancer development.