Discovery of a Novel Mechanism for Implementation of Epigenetic Memory
From left to right : Juliette Harris and Jacques Drouin
The understanding of genes is at the heart of research advances that lead to new therapies for many diseases. In this regard, innovative work in the laboratory of Dr. Jacques Drouin, Director of the Molecular Genetics Research Unit at the Montreal Clinical Research Institute (IRCM), revealed a new mechanism for implementing genetic memory, representing a major advance of knowledge in the field.
This work, by first author Juliette Harris (a PhD student at the IRCM), was just published in the journal Science Advances.
In detail
Epigenetic memory is the mechanism that maintains the stability of cell identity and it associated gene-expression program. This memory is implemented through DNA methylation. Active gene regulatory sequences are undermethylated and many mechanisms ensure that the pattern of DNA methylation is stably maintained. Pioneer transcription factors implement new cell fates and provide epigenetic memory by driving demethylation of target DNA.
Drouin’s team at the IRCM identified a novel mechanism that is used by a pioneer factor to establish epigenetic memory. This mechanism relies on direct inhibition of the system that normally maintains DNA demethylation. Cancer cells often have altered DNA methylation patterns responsible for dysregulated gene expression. The published data indicate how pioneer factor-dependent mechanisms may change DNA methylation patterns in these cells.
Why this is important
Since many cancers involve epigenetic alterations and pioneer factor-dependent mechanisms, this research opens new opportunities for development of targeted cancer therapies.
About Dr. Jacques Drouin's laboratory
The team is dedicated to unravelling the great mysteries surrounding how genes function and, conversely, what causes them to malfunction, as well as the consequences of these disturbances for human health.
A controlled expression of genes is essential for the development of complex organisms. This expression is the implementation of the plan encoded in our genome, and its deregulation, whether due to mutations or epigenetic disturbances, causes congenital malformations, more or less severe deficiencies, and cancer. The Molecular Genetics Research Unit studies these mechanisms, from their basic principles to their application in human health.
Acknowledgements
The work of the Molecular Genetics laboratory at the IRCM is supported by grants from the Canadian Institute of Health Research. Oxford Nanopore Technologies Inc contributed to the work by facilitating access to their latest technologies for direct sequencing of selected native DNA duplexes.
