Team
Epigenetics of Regeneration and Cancer (E-ReCa)

Dpt: Signaling through Chromatin

Our research activities

During development, stem cells proliferate and differentiate to compose somatic tissues. By tightly controlling gene expression, chromatin organization is both a defining component of cell identities and a barrier to transcriptional reprogramming that preserves cells from de-differentiation. Yet, following tissue loss or wound, there is a species-specific potential for large-scale regeneration often involving somatic cell regression into a pluripotent state followed by their proliferation and re-differentiation. While powerful to maintain tissue homeostasis, these mechanisms are also dangerous in that they offer a window of opportunity for certain cells to escape their programmed identity. Indeed, cancerous cells often acquire the capacity to overcome and exploit these chromatin barriers to cell transitions to bypass their somatic fate, become proliferative and acquire aberrant identities. Regeneration is therefore a double-edged sword, ensuring tissue integrity but also operating as a backdoor to cancer transformation. Our goal is to understand the epigenetic bases of cell plasticity in regeneration and cancer ultimately seeking to identify actionable mechanisms to facilitate regeneration while avoiding tumorigenesis. Our laboratory studies these mechanisms by implementing high-resolution methods in epigenomics and microscopy focusing on two model cases: hormone dependency in breast cancers and leg regeneration in an insect, the two-spotted cricket Gryllus bimaculatus.
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Guillermo ORSI

Team leader

04 76 54 95 25 

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Our research axes

Cancer cells change their epigenome to escape somatic control. Focusing on breast cancer, we want to understand how this adaptation conditions their identity and determines their aggressivity as well as their response to treatments.

As many other insects and arthropods, crickets have the capacity to fully regenerate their legs if amputated. We want to understand the epigenomic mechanisms allowing cells to change their identities several times to ensure this spectacular process goes smoothly.

Polycomb complexes repress selected target genes to define cell identity across eukaryotes. Via our different model systems and collaborations, we ask how Polycomb proteins target DNA selectively and conditionally in different species.

Our major publications

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Three classes of epigenomic regulators converge to hyperactivate the essential maternal gene deadhead within a heterochromatin mini-domain

Torres-Campana D, Horard B, Denaud S, Benoit G, Loppin B, Orsi GA.

PLoS Genet 2022 Jan 4;18(1):e1009615. doi: 10.1371/journal.pgen.1009615

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The Lid/KDM5 histone demethylase complex activates a critical effector of the oocyte-to-zygote transition

Torres-Campana D#, Kimura S#, Orsi GA, Horard B, Benoit G, Loppin B.

PLoS Genet 2020 Mar 5;16(3):e1008543. doi:10.1371/journal.pgen.1008543

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Two HIRA- dependent pathways mediate H3.3 de novo deposition and recycling during transcription

Torné J, Ray-Gallet D, Boyarchuk E, Garnier M, Le Baccon P, Coulon A, Orsi GA*, Almouzni…

Nat Struct Mol Biol. 2020 Nov;27(11):1057-1068. doi: 10.1038/s41594-020-0492-7

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High-resolution visualization of H3 variants during replication reveals their controlled recycling

Clément C, Orsi GA, Gatto A, Boyarchuk E, Forest A, Hajj B, Miné-Hattab J, Garnier M,…

Nat Commun 2018 Aug 9;9(1):3181. doi:10.1038/s41467-018-05697-1

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Imaging Newly Synthesized and Old Histone Variant Dynamics Dependent on Chaperones Using the SNAP-Tag System

Torné J, Orsi GA, Ray-Gallet D, Almouzni G.

Methods Mol Biol 2018 1832:207-221. doi: 10.1007/978-1-4939-8663-7_11. PMID: 30073529.

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Mapping regulatory factors by immunoprecipitation from native chromatin

Orsi GA#, Kasinathan S#, Zentner GE, Henikoff S, Ahmad K.

Curr Protoc Mol Biol 2015 Apr 1;110:21.31.1-21.31.25. doi: 10.1002/0471142727.mb2131s110.

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High-resolution mapping defines the cooperative architecture of Polycombresponse elements

Orsi GA, Kasinathan S, Hughes KT, Saminadin-Peter S, Henikoff S, Ahmad K.

Genome Res 2014 May;24(5):809-20. doi:10.1101/gr.163642.113

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High-resolution mapping of transcription factor binding sites on native chromatin

Kasinathan S, Orsi GA, Zentner GE, Ahmad K, Henikoff S.

Nat Methods 2014 Feb;11(2):203-9. doi: 10.1038/nmeth.2766

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Drosophila Yemanuclein and HIRA cooperate for de novo assembly of H3.3-containing nucleosomes in the male pronucleus

Orsi GA, Algazeery A, Meyer RE, Capri M, Sapey-Triomphe LM, Horard B, Gruffat H, Couble…

PLoS Genet. 2013 9(2):e1003285. doi: 10.1371/journal.pgen.1003285.

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Nucleosome-depleted chromatin gaps recruit assembly factors for the H3.3 histone variant.

Schneiderman JI#, Orsi GA#, Hughes KT, Loppin B, Ahmad K.

Proc Natl Acad Sci U S A 2012 Nov 27;109(48):19721-6. doi: 10.1073/pnas.1206629109

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Our activities in pictures

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Our technologies

  • Cut&Run
  • MNase-seq
  • Stochastic Optical Reconstruction Microscopy (STORM)
  • Bioinformatics
  • Insect models