第9回頭脳循環セミナー - 名古屋市立大学大学院医学研究科・医学部

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Alterations of the Polycomb machinery
in cancers
O6YRaphaël Margueron )C
Junior Group leader, Curie Institute,
Developmental Biology and Genetics, France :;YVW<WV:T@UZ
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The control of cell identity entails a precise orchestration of gene expression
programs. Although transcription factors play a crucial role in the establishment
and maintenance of transcriptional networks, their action is constrained by
chromatin. This nucleoproteic structure is tightly controlled by the combination of
histone modifications, DNA methylation, histone variant deposition and
nucleosome occupancy. The proper orchestration of these modifications requires a
battery of enzymes, which precisely and dynamically regulate chromatin
structure.
Recent whole-genome sequencing of large numbers of cancers has revealed that
mutations of chromatin regulators is a recurrent theme across cancers yet it
remains poorly understood how these mutations lead to the impairment of
transcriptional programs. We are investigating this question in the context of the
Polycomb machinery, a crucial actor for the maintenance of cell identity. I will
present our studies aimed at understanding how the Polycomb machinery
function, the consequences of its alterations and the therapeutic potential of
modulating its activity.
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1. Uveal melanoma cells are resistant to EZH2 inhibition regardless of BAP1 status.
Nature Medicine, 577-8, 2016.
2. Impaired PRC2 activity promotes transcriptional instability and favors breast tumorigenesis.
Genes and Development, 2547-62, 29, 2015.
3. Jarid2 methylation via the PRC2 complex regulates H3K27me3 deposition during cell differentiation.
Molecular Cell, 769-83, 57, 2015.
4. Jarid2 Is Implicated in the Initial Xist-Induced Targeting of PRC2 to the Inactive X Chromosome.
Molecular Cell, 301-16, 57, 2014.
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