20-year epigenetics mystery solved
Thursday March 2nd 2023
A 20-year mystery of how epigenetic modifications act as traffic lights to control gene expression has finally been uncovered, British scientists have announced.
The findings from the major new study by scientists at The Institute of Cancer Research, London, could eventually lead to new targets for cancer drugs, the researchers say.
Writing in the latest edition of *Nature*, the team shows how H3K4me3, a key epigenetic signal, determines when and how DNA should be read and translated into proteins within our cells.
Study leader Professor Kristian Helin, chief executive of The Institute of Cancer Research and a world leader in epigenetics, said: "Our study offers a fundamental new understanding of epigenetics, a very exciting and still largely underexplored area of cancer research.
“We have solved a 20-year-old puzzle by discovering how a well-known epigenetic modification controls gene expression. Because the enzymes determining the level of H3K4me3 in the cell frequently are found mutated in cancer, our studies could have implications for understanding and treating cancer.”
The team found H3K4me3 ensures genes are transcribed and activated in a controlled way and at the right time – in the same way traffic lights regulate vehicles.
This breakthrough can also help them to shed new light on the development of cancer and the role played by a breakdown in the regulation of gene activity.
Although it has long been known that the enzymes placing H3K4me3 are crucial for normal cell development, as well as being linked to some cancers, it was not understood what the chemical tag does.
Using mouse stem cells and genetic and biochemical experiments in the lab, researchers found the H3K4me3 modification is essential for regulating how and when our genes are expressed.
By regulating the flow of RNA polymerase II, a protein complex that reads and decodes DNA, H3K4me3 determines when gene expression should start and the speed at which it runs.
When it gives the green light, H3K4me3 allows RNA polymerase II to move along DNA, transcribing it into RNA as it moves. But without H3K4me3, RNA polymerase II gets stuck at specific points on the DNA, creating a hold-up and slowing down transcription.
“Drugs targeting these ‘traffic lights’, or epigenetic modifications, such as H3K4me3, are already being developed – and it is possible that they could one day become an effective way of treating cancer patients,” said Professor Helin.
“This is an exciting new avenue for cancer research, and we believe our findings will pave the way for more effective development of these epigenetic drugs.”
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