Abstract
Controlling the functional dynamics of DNA within living cells is essential in biomedical research. Epigenetic modifications such as DNA methylation play a key role in this endeavour. DNA methylation can be controlled by genetic means. Yet there are few chemical tools available for the spatial and temporal modulation of this modification. Herein, we present a small‐molecule approach to modulate DNA methylation with light. The strategy uses a photo‐tuneable version of a clinically used drug (5‐aza‐2′‐deoxycytidine) to alter the catalytic activity of DNA methyltransferases, the enzymes that methylate DNA. After uptake by cells, the photo‐regulated molecule can be light‐controlled to reduce genome‐wide DNA methylation levels in proliferating cells. The chemical tool complements genetic, biochemical, and pharmacological approaches to study the role of DNA methylation in biology and medicine.
Highlights
Ha Phuong Nguyen, Sabrina Stewart, Mikiembo N
Controlling the functional dynamics of DNA within living cells is essential in biomedical research
Epigenetic modifications such as DNA methylation play a key role in this endeavour
Summary
Ha Phuong Nguyen, Sabrina Stewart, Mikiembo N. Driven by the growing importance of DNA methylation in biomedical research, there is a strong interest to experimentally lower or increase methylation levels[17,18,19,20,21,22,23] to study, for example, the role of epigenetic reprogramming in tissue development or regenerative medicine.[24,25] Optical control is of particular relevance given the high spatial and temporal resolution of light.
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