Rougeulle group

Non coding RNA, differentiation and development

EMBO XCI meeting. Berlin 2023

© Rougeulle Team

Research in the Rougeulle lab focuses on the emblematic process of X chromosome inactivation, with the aim to elucidate how such a chromosome-wide epigenetic silencing is achieved and regulated in various mammalian species. More generally, we are interested in the epigenetic control of gene expression in relation to cell identity and fate, the contribution of long noncoding RNA genes and transposable elements to these processes and the plasticity of epigenetic regulations in evolution.

We use a variety of mouse and primate pluripotent stem cells and their differentiated derivatives to recapitulate key developmental stages and cellular states. Our experimental strategy combines genome engineering (CRISPR) with single cell analyses, large scale transcriptomic and epigenomic investigations and 3D topological studies.

Our research projects :

Human X-inactivation in a dish                                                     

Description

X chromosome inactivation is critical for women development and linked to sex-specific susceptibilities to various diseases. To understand how XCI contributes to male-female differences, we model, in vitro, key steps of X-inactivation using, as an entry point, Human Embryonic Stem cells (hESC). hESC are reprogrammed to discover how XCI is initially established during the first days of embryonic development with a particular focus on the role of structural noncoding RNAs such as XIST and XACT. hESC are differentiated into specific cell types to assess the plasticity of XCI in distinct somatic tissues, including the hematopoietic compartment and organized tissue through the use of organoids.

Evolution of X-inactivation across primates

Description

Remarkable differences exist in the way X chromosome inactivation is set up between human and mouse in connection with drastically different network of regulatory lncRNA genes which our group contributed to decipher. We are now exploring phenotypic and mechanistic variability in X-inactivation across primates using non-human primate pluripotent stem cells to probe the degree of genetic and epigenetic innovation across a limited timescale, and the contribution of the noncoding genome to such evolution.

Plasticity of the noncoding genome

Description

The noncoding genome participates to the establishment of gene expression programs, and, as such, to cell identity and fate. It encompasses a vast repertoire of lncRNA genes (LRGs) – a fraction of which derives from endogenous retroviruses – whose function may be conveyed by distinct modules, such as the RNA itself, the genomic locus, the act of transcription, or any downstream smaller RNA by-products. X-inactivation is a striking example of a process controlled by LRGs acting at multiple levels and through diverse mechanisms. Our aim is to explore LRG’s versatility to understand whether a given LRG could play multiple functions in various developmental and cellular contexts, and how the underlying mechanisms may vary accordingly.

 

 

Publications

2024

  • Huret C., Ferrayé L., David A. Mohamed M., Valentin N., Charlotte F., Savignac M., Goodhardt M., Guéry J-C.,Rougeulle C. and Morey C. Altered X-chromosome inactivation predisposes to autoimmunity . Science Advances, 2024 May

2023

  • Rosspopoff O,  Cazottes E, Huret C, Loda A, Collier A, Casanova M, Rugg-Gunn P, Heard E, Ouimette JF, Rougeulle C. Species-specific regulation of XIST by the JPX/FTX orthologs . Nucleic Acids Research, 2023 Feb

2022

2021  

 2020

2019

  • Casanova MMoscatelli MChauvière LÉHuret CSamson JLiyakat Ali TMRosspopoff ORougeulle C. A primate-specific retroviral enhancer wires the XACT lncRNA into the core pluripotency network in humans. Nat Commun. 2019 Dec 11;10(1):5652.

2018

  • Furlan G, Gutierrez Hernandez N, Huret C, Galupa Rvan Bemmel JG, Romito A, Heard E, Morey C, Rougeulle C.  The Ftx Noncoding Locus Controls X Chromosome Inactivation Independently of Its RNA Products. Mol Cell. 2018 Apr 20. pii: S1097-2765(18)30227-2.

2017

  • Vallot C., Patrat C., Collier AJ., Huret C., Casanova M.Liyakat Ali TM.Tosolini M., Frydman N., Heard E., Rugg-Gunn P.J.and Rougeulle C. Competing action of XIST and XACT noncoding RNAs in the control of X chromosome activity during human early development. Cell Stem Cell. 2017 Jan 5;20(1):102-111.  

2016

  • Vallot C.,  Ouimette JF.Rougeulle C. Establishment of X chromosome inactivation and epigenomic features of the inactive X depend on cellular contexts.  Bioessays. 2016 Sep;38(9):869-80
  • Ouimette JF, Rougeulle C. How Many Non-coding RNAs Does It Take to Compensate Male/Female Genetic Imbalance?  Adv Exp Med Biol. 2016;886:33-49

2015

  • Vallot C*, Ouimette JF*, Makhlouf M, Féraud O, Pontis J, Côme J, Martinat C, Bennaceur-Griscelli A, Lalande M, Rougeulle C. Erosion of X Chromosome Inactivation in Human Pluripotent Cells Initiates with XACT Coating and Depends on a Specific Heterochromatin Landscape.Cell Stem Cell. 2015 May 7;16(5):533-46.

2014

  • Makhlouf M.*, Ouimette JF.*, Oldfield A.*, Navarro P., Neuillet D. and Rougeulle C. A prominent and conserved role for YY1 in Xist transcriptional activation. Nat Commun. 2014 Sep 11;5:4878.

2013

  • Häfner S. and Rougeulle C. La matière noire du génome. Pour la Science, 81: 58-63.
  • Vallot C., Huret C., Lesecque Y., Resch A., Oudrhiri N., Bennaceur-Griscelli A., Duret L. and Rougeulle C. XACT, a long non-coding transcript coating the active X chromosome in human pluripotent cells. Nat Genet. 2013 Mar;45(3):239-41.​

2012

2011

2010

  • Navarro P., Oldfield A., Legoupi J., Festuccia N., Dubois A., Attia M., Schoorlemmer J., Rougeulle C., Chambers I. and Avner P. Molecular coupling of Tsix regulation and pluripotency. Nature 2010 Nov 18;468(7322):457-60.​
  • Mitjavila-Garcia M., Bonnet M.L., Yates F., Haddad R., Oudrhiri N., Féraud O., Magniez A., Vallot C., Makhlouf M., Rougeulle C., Bennaceur-Griscelli A. and Turhan A.G. Partial reversal of the methylation pattern of X-linked gene HUMARA during hematopoietic differentiation of human embryonic stem cells. J Mol Cell Biol. 2010 Oct;2(5):291-8.​

2009

  • Navarro P., Chantalat S., Foglio M., Chureau C., Vigneau S., Clerc P. Avner P. and Rougeulle C. A role for non-coding Tsix transcription in partitioning chromatin domains within the mouse X-inactivation centre. Epigenetics Chromatin. 2009 Jul 20;2(1):8.​
Members
profil pic AlfeghalyCharbel

Charbel Alfeghaly

Post-doctoral fellow (CDD CNRS ERC Xcycle)

charbel.alfeghaly@u-paris.fr

+33(0)157278929

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profil pic BrouilletJeanne

Jeanne Brouillet

Bioinformatic engineer (CDD CNRS ERC XCycle)

brouillet.jeanne@parisepigenetics.com

+33(0)157278930

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profil pic CarrilloLeo

Leo Carrillo

PhD Student (Université Paris Cité)

leo.carrillo@etu.u-paris.fr

+33(0)157278930

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profil pic DubourgClara

Clara Dubourg

Engineer (CDD CNRS ERC XCycle)

clara.dubourg@cnrs.fr

+33(0)157278930

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profil pic FacchinelloRomina

Romina Facchinello

PhD student (Université Paris Cité)

romina.facchinello@etu.u-paris.fr

+33 (0)157278930

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profil pic HuretChristophe

Christophe Huret

Lab Manager | Vectorology platform manager (Université Paris Cité)

christophe.huret@u-paris.fr

+33(0)157278929

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profil pic MoreyCéline

Céline Morey

Senior researcher (INSERM)

celine.morey@univ-paris-diderot.fr

+33(0)157278929

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profil pic OuimetteJean-Francois

Jean-Francois Ouimette

Assistant Professor (Université Paris Cité)

jean-francois.ouimette@u-paris.fr

+33(0)157278929

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profil pic PiquerasCarla

Carla Piqueras

PhD student (Université Paris Cité)

carla.piqueras@etu.u-paris.fr

+33(0)157278930

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profil pic RougeulleClaire

Claire Rougeulle

Team Leader | Deputy Director (CNRS)

claire.rougeulle@u-paris.fr

+33(0)157278924

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Alumni

 

Megha Balachandra – Master 2 student

Naïs Boistol – BTS student

Juliette Boni – Master 1 student

Charlie Bouchu – Master 1 student

Miguel Casanova – Post-Doc

Gaël Castel – Bionformatic engineer

Louis Chauvière – PhD student

Solène Coste – Master 2 student

Arnaud Divol – Master 2 student

Giulia Furlan – PhD student / transitional Post Doc

Angélique Galvani – Lecturer

Elena Gomez Garcia – Licence 2 Erasmus student

Nancy Gutierrez Hernandez – Master 1 student

Sophia Häfner – PhD student

Margot Hully – Master 1 ENS student

Yoann Kovacs – Master 2 student

Ibrahim Lafi – Master 1 Polytechnique student

Alexia Le Barch – Master 1 Polytechnique Student

Tharvesh Moideen Liyakat Ali – Bioinformatic engineer

Charlie London – Engineer

Kasturi Mahadik – Post Doc

Mélanie Makhlouf – PhD student / Post Doc

Madeleine Moscatelli – PhD student / transitional Post Doc

Damien Neuillet – Assistant engineer

Andrew Oldfield – PhD student

Antonio Romito – Post Doc

Olga Rosspopoff – PhD student / transitional Post Doc

Julia Samson – Master 2 student

Samantha Sheng – Post Doc

Matteo Tossolini – Master 2 student

Céline Vallot – researcher CNRS

Valentina Varriale – Master 1 Polytechnique student

Funding

         

Contact

Claire ROUGEULLE, PhD, HDR, DR1 – CNRS
CNRS – Epigenetics and Cell Fate – UMR7216
Université Paris Cité
Bat Lamarck, 4ème étage. Case courrier 7042
35, rue Hélène BRION
75205 Paris Cedex 13

Tél : 33 (0)1 5727 8924
Fax : 33 (0)1 5727 8911
Email : claire.rougeulle@u-paris.fr

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