Artificial Catalysts For Epigenetics Without Enzymes

Scientists in Japan have performed DNA acetylation in living cells using chemical catalysts instead of biological enzymes.

AsianScientist (Aug. 28, 2017) – Researchers at the University of Tokyo have developed an artificial catalyst system that can selectively modify protein-DNA complexes in cells. Their work is published in Chem.

In cells, DNA is bound to proteins known as histones, forming higher-ordered structures called nucleosomes. Enzymes—cellular catalysts—carry out various chemical modifications such as acetylation on histones. Histone acetylation is an important epigenetic mark that regulates gene expression in living cells. Various genetic disorders, including certain types of cancer, are linked to abnormalities in the regulation of histone acetylation.

In this study, a research group led by Professor Motomu Kanai at the University of Tokyo, have performed histone acetylation synthetically without using enzymes, instead relying on an artificial catalyst system composed of chromatin-binding catalysts and acetyl donors.

The group found that the biochemical properties of nucleosomes were modified by synthetic histone acetylation, resulting in gene transcription. In addition, by changing the acetyl donor to a malonic acid donor, the catalyst system could also carry out malonylation, hinting at broader possibilities for promoting other types of chemical modifications on histones.

The artificial catalyst system holds promise for ‘catalysis medicine,’ an emerging approach in which enzymes functions are substituted by chemical reactions promoted by non-biological entities. The system can also be used to probe the underlying functions of biochemical processes in living cells, making it a useful tool for treating diseases and advancing medicine in the future.

“This is the first step toward achieving ‘catalysis medicine,’ the new medical concept that we are pursuing, and we will continue our efforts to develop better catalysts,” said Assistant Professor Shigehiro Kawashima of the University of Tokyo who co-authored the paper.

“Life originates from a network of molecules and chemical reactions. We will apply the power of chemistry to contribute to life science and health care,” added Assistant Professor Kenzo Yamatsugu of the University of Tokyo who also contributed to the work.

The article can be found at: Ishiguro et al. (2017) Synthetic Chromatin Acylation by an Artificial Catalyst System.


Source: University of Tokyo; Photo: Shutterstock.
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