Epigenetics, RNA, and Genome Dynamics

Emanuelle Manck
11/05/2021
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The exploration of all dimensions of the genome is an essential line of research at Institut Curie. It is indispensable to a better understanding of how cancer works, since all cancers result from the alteration of the genetic material of a cell.
image equipe Descroix

Suivi in vivo de molécules uniques de myosine V marquées par des nanocristaux fluorescents (quantum dots en anglais). En A : chaque nanocristal est visible sous la forme d’un point rouge…

Epigenetics

Epigenetics is the study of the chemical modifications that regulate gene expression without changing the DNA sequence: DNA methylation, histone acetylation, chromatin restructuring, the presence of non-coding RNAs, etc. Epigenetic mechanisms are mainly involved in the normal processes of cell differentiation and development. Institut Curie Research Center is working towards a deeper understanding of epigenetic regulation, with a focus on revealing the role of enzymes in chemical epigenetic modifications. Cancer can also be seen as a cellular identity problem, both genetic and epigenetic, showing frequent enzymatic mutation and aberrant or aggressive phenotype acquisition. We can regard such mutations as therapeutic targets.

We study single-cell epigenetic transitions to determine the best moment to target them and which molecules to combine them with in targeted therapies

says Céline Vallot, head of the Dynamics of epigenetic plasticity in cancer research team.

RNA

Observing RNAs more closely allows us to better understand both genomic transcription into messenger RNAs (mRNA) and proteins, and the role of the noncoding genome in normal biological and pathological processes. Institut Curie Research Center teams research RNA regulation and deregulation--whether in the maturation of mRNAs, the translation of mRNA into proteins, or in mRNA-protein interactions--in healthy cells, in cancer cases, and in cases undergoing cancer treatment. They also research the transcription of non-coding RNAs and transposable elements which may be involved in DNA damage response, the characteristics of cancer, the formation of metastases, and certain forms of resistance to cancer therapies. All this innovative research can play a role in improving cancer outcomes

 

We have discovered more than a thousand RNA-binding proteins: we need to better understand the role they play in cancers so we can label them as diagnostic or prognostic markers and, possibly, as therapeutic targets

says Stéphan Vagner, director of the Genome Integrity, RNA and Cancer unit and head of the RNA Biology, Signalling and Cancer (U1278) research team.

Genome Dynamics

Genetic information is not etched in stone. Not only does the genome have to be duplicated for the purposes of cell division and heredity, wherein it is continuously maintained and corrected for abnormalities, but over the lifespan of the cell and the body, genetic expression is regulated, controlled, and variable. Genomic dynamics are both temporal and spatial: temporally, there must be a balance between the inheritance, conservation, and transmission of genetic information, but spatially, the various regions of the genome must be organized, appropriately sized, and made accessible. Research Center teams are particularly interested in the compaction and opening of certain DNA zones, DNA conservation during replication, and the destabilization of DNA by mutation. They also research DNA repair, either through recombination during cell division or through the intervention of the P53 “guardian” protein, and the non-coding genes that play a crucial role in genome integrity and expression.

 

Today, high throughput sequencing and bioinformatics afford us a global view of cellular genetic information at a given time to help us better answer questions about genome dynamics

says Antonin Morillon, director of the Dynamics of Genetic Information: Fundamental Bases and Cancer (DIG-Cancer) unit and head of the Non-coding RNA, Epigenetics, and Genomes Fluidity research team.