Chroma Therapeutics Limited

Tony Kouzarides

Helena Santos-Rosa

This invention relates to the methylation of histones, in particular to a previously uncharacterised group of histone H3 methylases which comprise a SET domain and which methylate either lysine 4 within the amino tail of histone H3 or within the histone H3 core. Methylation by these methylases, in particular trimethylation, is shown to be important for transcriptional activity.

Methods and means of histone methylation

P/CAF interacts with and acetylates E2F, this acetylation affecting ability of E2F to stimulate transcription. Interaction between P/CAF and E2F and acetylation of E2F by P/CAF are modulated, affecting ability of E2F to stimulate transcription, induction of S-phase in cells, oncogenicity of cells, and induction of apoptosis in cells. Agents are obtained for treatment of disorders of cell growth.

Assays, methods and means for modulating e2f activity

CBP histone acetyltransferase acetylates Importin &agr;, affecting ability of Importin &agr; to translate into the nucleus and import a cargo protein. Assays identify substances which modulate interaction between CBP and Importin &agr; and acetylation of Importin &agr; by CBP. Substances identified in the assays are useful for treatment of disorders in which Imporin &agr; plays a role.

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Cambridge, United Kingdom

Tony Kouzarides