Philippe ARNAUD

DR2 CNRS

Resume

Philippe ARNAUDprofile picture

2012- Team leader at GReD -CNRS Staff scientist (DR2)

   “ Epigenetic control of cell fate determination”

2004-2011 CNRS Staff scientist (CR)- IGMM UMR5535, Montpellier- Dr. Robert Feil’s team

  “Role of histone modifications in genomic imprinting”.

2000-2003  Post-Doct (Marie Curie Fellow) - Babraham Institute, Cambridge,  UK- GKelsey’s Team

   "Epigenetic control opf genomic imprinting".

1996-2000  Ph.D  – Université Blaise Pascal, Clermont-Ferrand.J.M Deragon’s Team

     "DNA methylation and Host defence hypothesis: The plant SINE S1Bn as a model".

Research

Our thematic aims to address if and how histone modifications could be part of a –short-term– flexible epigenetic silencing mechanism, potentially involved in cell fate decisions. In this purpose, we are focusing on the so called bivalent chromatin structures. These structures are unusual because their histone H3 is concomitantly marked by the “active” H3K4me and the “repressive” H3K27me3 modifications. Bivalent domains were initially detected at promoters of many genes in both human and mouse ES cells. In the proposed model, bivalent chromatin domains act to repress gene transcription through H3K27me3, while keeping genes "poised" for alternative fates for when a differentiation pathway is induced by specific developmental cues However, their precise role in development remains controversial because probing the function of bivalent domains in developing organisms remains a challenge.

To gain insight into this important issue we  analyse bivalency in two well defined frames, accounting for both normal and pathological contexts, namely in the genomic imprinting developmental process and in glioma tumors.

Publications

  • 2019
    • F. Court, E. Le Boiteux, A. Fogli, M. Muller-Barthelemy, C. Vaurs-Barriere, E. Chautard, B. Pereira, J. Biau, J. Kemeny, T. Khalil, L. Karayan-Tapon, P. Verrelle and P. Arnaud, “Transcriptional alterations in glioma result primarily from DNA methylation-independent mechanisms.”, Genome Res., vol. 29 (10) , pp. 1605–1621, 2019.
  • 2018
    • S. Maupetit-Mehouas, F. Court, C. Bourgne, A. Guerci-Bresler, P. Cony-Makhoul, H. Johnson, G. Etienne, P. Rousselot, D. Guyotat, A. Janel, E. Hermet, S. Saugues, J. Berger, P. Arnaud and M. Berger, “DNA methylation profiling reveals a pathological signature that contributes to transcriptional defects of CD34(+) CD15(-) cells in early chronic-phase chronic myeloid leukemia.”, Molecular oncology, vol. 12 (6) , pp. 814–829, 2018.
    • A. Xavier-Magalhaes, C. Goncalves, A. Fogli, T. Lourenco, M. Pojo, B. Pereira, M. Rocha, M. Lopes, I. Crespo, O. Rebelo, H. Tao, J. Lima, R. Moreira, A. Pinto, C. Jones, R. Reis, J. Costello, P. Arnaud, N. Sousa and B. Costa, “The long non-coding RNA HOTAIR is transcriptionally activated by HOXA9 and is an independent prognostic marker in patients with malignant glioma.”, Oncotarget, vol. 9 (21) , pp. 15740–15756, 2018.
    • M. Pinson, R. Pogorelcnik, F. Court, P. Arnaud and C. Vaurs-Barriere, “CLIFinder: identification of LINE-1 chimeric transcripts in RNA-seq data.”, Bioinformatics (Oxford, England), vol. 34 (4) , pp. 688–690, 2018.
  • 2017
    • A. Fogli, M. Demattei, L. Corset, C. Vaurs-Barriere, E. Chautard, J. Biau, J. Kemeny, C. Godfraind, B. Pereira, T. Khalil, N. Grandin, P. Arnaud, M. Charbonneau and P. Verrelle, “Detection of the alternative lengthening of telomeres pathway in malignant gliomas for improved molecular diagnosis.”, Journal of neuro-oncology, 2017.
    • F. Court and P. Arnaud, “An annotated list of bivalent chromatin regions in human ES cells: a new tool for cancer epigenetic research.”, Oncotarget, vol. 8 (3) , pp. 4110–4124, 2017.
  • 2016
    • T. Bouschet, E. Dubois, C. Reynes, S. Kota, S. Rialle, S. Maupetit-Mehouas, M. Pezet, A. Le Digarcher, S. Nidelet, V. Demolombe, P. Cavelier, C. Meusnier, C. Maurizy, R. Sabatier, R. Feil, P. Arnaud, L. Journot and A. Varrault, “In Vitro Corticogenesis from Embryonic Stem Cells Recapitulates the In Vivo Epigenetic Control of Imprinted Gene Expression.”, Cerebral cortex (New York, N.Y. : 1991), 2016.
    • S. Maupetit-Mehouas, B. Montibus, D. Nury, C. Tayama, M. Wassef, S. Kota, A. Fogli, F. Cerqueira Campos, K. Hata, R. Feil, R. Magueron, K. Nakabayashi, F. Court and P. Arnaud, “Imprinting control regions (ICRs) are marked by mono-allelic bivalent chromatin when transcriptionally inactive.”, Nucleic Acids Res., vol. 44 (2) , pp. 621-635, 2016.
    • A. Fogli, E. Chautard, C. Vaurs-Barriere, B. Pereira, M. Muller-Barthelemy, F. Court, J. Biau, A. Almeida Pinto, J. Kemeny, T. Khalil, L. Karayan-Tapon, P. Verrelle, B. Costa and P. Arnaud, “The tumoral A genotype of the MGMT rs34180180 single-nucleotide polymorphism in aggressive gliomas is associated with shorter patients' survival.”, Carcinogenesis, vol. 37 (2) , pp. 169-176, 2016.
  • 2015
    • L. Veselovska, S. Smallwood, H. Saadeh, K. Stewart, F. Krueger, S. Maupetit-Mehouas, P. Arnaud, S. Tomizawa, S. Andrews and G. Kelsey, “Deep sequencing and de novo assembly of the mouse oocyte transcriptome define the contribution of transcription to the DNA methylation landscape.”, Genome biology, vol. 16 (1) , pp. 209, 2015.
  • 2014
    • S. Kota, D. Lleres, T. Bouschet, R. Hirasawa, A. Marchand, C. Begon-Pescia, I. Sanli, P. Arnaud, L. Journot, M. Girardot and R. Feil, “ICR noncoding RNA expression controls imprinting and DNA replication at the Dlk1-Dio3 domain.”, Dev. Cell, vol. 31 (1) , pp. 19–33, 2014.
  • 2013
  • 2012
    • A. Henckel, K. Chebli, S. Kota, P. Arnaud and R. Feil, “Transcription and histone methylation changes correlate with imprint acquisition in male germ cells.”, EMBO J., vol. 31 (3) , pp. 606–15, 2012-02-01 2012.
    • I. Iglesias-Platas, A. Martin-Trujillo, D. Cirillo, F. Court, A. Guillaumet-Adkins, C. Camprubi, D. Bourc'his, K. Hata, R. Feil, G. Tartaglia, P. Arnaud and D. Monk, “Characterization of novel paternal ncRNAs at the Plagl1 locus, including Hymai, predicted to interact with regulators of active chromatin.”, PLoS ONE, vol. 7 (6) , pp. e38907, 2012.
  • 2011
    • O. Ganier, S. Bocquet, I. Peiffer, V. Brochard, P. Arnaud, A. Puy, A. Jouneau, R. Feil, J. Renard and M. Mechali, “Synergic reprogramming of mammalian cells by combined exposure to mitotic Xenopus egg extracts and transcription factors.”, Proc. Natl. Acad. Sci. U.S.A., vol. 108 (42) , pp. 17331–6, 2011.
    • D. Monk, P. Arnaud, J. Frost, A. Wood, M. Cowley, A. Martin-Trujillo, A. Guillaumet-Adkins, I. Iglesias Platas, C. Camprubi, D. Bourc'his, R. Feil, G. Moore and R. Oakey, “Human imprinted retrogenes exhibit non-canonical imprint chromatin signatures and reside in non-imprinted host genes.”, Nucleic Acids Res., vol. 39 (11) , pp. 4577–86, 2011.
  • 2010
    • O. Alder, F. Lavial, A. Helness, E. Brookes, S. Pinho, A. Chandrashekran, P. Arnaud, A. Pombo, L. O'Neill and V. Azuara, “Ring1B and Suv39h1 delineate distinct chromatin states at bivalent genes during early mouse lineage commitment.”, Development, vol. 137 (15) , pp. 2483–92, 2010.
    • A. Henckel and P. Arnaud, “Genome-wide identification of new imprinted genes.”, Brief Funct Genomics, vol. 9 (4) , pp. 304–14, 2010.
    • P. Arnaud, “Genomic imprinting in germ cells: imprints are under control.”, Reproduction, vol. 140 (3) , pp. 411–23, 2010.
  • 2009
    • D. Monk, P. Arnaud, J. Frost, F. Hills, P. Stanier, R. Feil and G. Moore, “Reciprocal imprinting of human GRB10 in placental trophoblast and brain: evolutionary conservation of reversed allelic expression.”, Hum. Mol. Genet., vol. 18 (16) , pp. 3066–74, 2009.
    • A. Henckel, K. Nakabayashi, L. Sanz, R. Feil, K. Hata and P. Arnaud, “Histone methylation is mechanistically linked to DNA methylation at imprinting control regions in mammals.”, Hum. Mol. Genet., vol. 18 (18) , pp. 3375–83, 2009.
  • 2008
    • D. Monk, A. Wagschal, P. Arnaud, P. Muller, L. Parker-Katiraee, D. Bourc'his, S. Scherer, R. Feil, P. Stanier and G. Moore, “Comparative analysis of human chromosome 7q21 and mouse proximal chromosome 6 reveals a placental-specific imprinted gene, TFPI2/Tfpi2, which requires EHMT2 and EED for allelic-silencing.”, Genome Res., vol. 18 (8) , pp. 1270–81, 2008.
    • L. Sanz, S. Chamberlain, J. Sabourin, A. Henckel, T. Magnuson, J. Hugnot, R. Feil and P. Arnaud, “A mono-allelic bivalent chromatin domain controls tissue-specific imprinting at Grb10.”, EMBO J., vol. 27 (19) , pp. 2523–32, 2008.
  • 2007
    • A. Henckel, S. Toth and P. Arnaud, “Early mouse embryo development: could epigenetics influence cell fate determination?”, BioEssays : news and reviews in molecular, cellular and developmental biology, vol. 29 (6) , pp. 520–4, 2007.
    • L. Parker-Katiraee, A. Carson, T. Yamada, P. Arnaud, R. Feil, S. Abu-Amero, G. Moore, M. Kaneda, G. Perry, A. Stone, C. Lee, M. Meguro-Horike, H. Sasaki, K. Kobayashi, K. Nakabayashi and S. Scherer, “Identification of the imprinted KLF14 transcription factor undergoing human-specific accelerated evolution.”, PLoS Genet., vol. 3 (5) , pp. e65, 2007.
    • A. Wagschal, K. Delaval, M. Pannetier, P. Arnaud and R. Feil, “Chromatin Immunoprecipitation (ChIP) on Unfixed Chromatin from Cells and Tissues to Analyze Histone Modifications.”, CSH protocols, vol. 2007 , pp. pdb.prot4767, 2007.
    • A. Wagschal, K. Delaval, M. Pannetier, P. Arnaud and R. Feil, “PCR-Based Analysis of Immunoprecipitated Chromatin.”, CSH protocols, vol. 2007 , pp. pdb.prot4768, 2007.
  • 2006
    • D. Monk, R. Sanches, P. Arnaud, S. Apostolidou, F. Hills, S. Abu-Amero, A. Murrell, H. Friess, W. Reik, P. Stanier, M. Constancia and G. Moore, “Imprinting of IGF2 P0 transcript and novel alternatively spliced INS-IGF2 isoforms show differences between mouse and human.”, Hum. Mol. Genet., vol. 15 (8) , pp. 1259–69, 2006.
    • D. Monk, P. Arnaud, S. Apostolidou, F. Hills, G. Kelsey, P. Stanier, R. Feil and G. Moore, “Limited evolutionary conservation of imprinting in the human placenta.”, Proc. Natl. Acad. Sci. U.S.A., vol. 103 (17) , pp. 6623–8, 2006.
    • P. Arnaud, K. Hata, M. Kaneda, E. Li, H. Sasaki, R. Feil and G. Kelsey, “Stochastic imprinting in the progeny of Dnmt3L-/- females.”, Hum. Mol. Genet., vol. 15 (4) , pp. 589–98, 2006.
    • P. Arnaud and R. Feil, “MEDEA takes control of its own imprinting.”, Cell, vol. 124 (3) , pp. 468–70, 2006.
  • 2005
    • P. Arnaud and R. Feil, “Epigenetic deregulation of genomic imprinting in human disorders and following assisted reproduction.”, Birth defects research. Part C, Embryo today : reviews, vol. 75 (2) , pp. 81–97, 2005.
  • 2004
    • R. Smith, P. Arnaud and G. Kelsey, “Identification and properties of imprinted genes and their control elements.”, Cytogenetic and genome research, vol. 105 (2-4) , pp. 335–45, 2004.
  • 2003
    • D. Monk, R. Smith, P. Arnaud, M. Preece, P. Stanier, C. Beechey, J. Peters, G. Kelsey and G. Moore, “Imprinted methylation profiles for proximal mouse chromosomes 11 and 7 as revealed by methylation-sensitive representational difference analysis.”, Mammalian genome : official journal of the International Mammalian Genome Society, vol. 14 (12) , pp. 805–16, 2003.
    • C. Coombes, P. Arnaud, E. Gordon, W. Dean, E. Coar, C. Williamson, R. Feil, J. Peters and G. Kelsey, “Epigenetic properties and identification of an imprint mark in the Nesp-Gnasxl domain of the mouse Gnas imprinted locus.”, Molecular and cellular biology, vol. 23 (16) , pp. 5475–88, 2003.
    • P. Arnaud, D. Monk, M. Hitchins, E. Gordon, W. Dean, C. Beechey, J. Peters, W. Craigen, M. Preece, P. Stanier, G. Moore and G. Kelsey, “Conserved methylation imprints in the human and mouse GRB10 genes with divergent allelic expression suggests differential reading of the same mark.”, Hum. Mol. Genet., vol. 12 (9) , pp. 1005–19, 2003.
  • 2002
    • R. Smith, P. Arnaud, G. Konfortova, W. Dean, C. Beechey and G. Kelsey, “The mouse Zac1 locus: basis for imprinting and comparison with human ZAC.”, Gene, vol. 292 (1-2) , pp. 101–12, 2002.
  • 2001
    • P. Arnaud, Y. Yukawa, L. Lavie, T. Pelissier, M. Sugiura and J. Deragon, “Analysis of the SINE S1 Pol III promoter from Brassica; impact of methylation and influence of external sequences.”, Plant J., vol. 26 (3) , pp. 295–305, 2001.
  • 2000
    • P. Arnaud, C. Goubely, T. Pelissier and J. Deragon, “SINE retroposons can be used in vivo as nucleation centers for de novo methylation.”, Molecular and cellular biology, vol. 20 (10) , pp. 3434–41, 2000.
  • 1999
    • C. Goubely, P. Arnaud, C. Tatout, J. Heslop-Harrison and J. Deragon, “S1 SINE retroposons are methylated at symmetrical and non-symmetrical positions in Brassica napus: identification of a preferred target site for asymmetrical methylation.”, Plant molecular biology, vol. 39 (2) , pp. 243–55, 1999.
  • 1997
    • N. Gilbert, P. Arnaud, A. Lenoir, S. Warwick, G. Picard and J. Deragon, “Plant S1 SINEs as a model to study retroposition.”, Genetica, vol. 100 (1-3) , pp. 155–60, 1997.
  • 1996
    • J. Deragon, N. Gilbert, L. Rouquet, A. Lenoir, P. Arnaud and G. Picard, “A transcriptional analysis of the S1Bn (Brassica napus) family of SINE retroposons.”, Plant molecular biology, vol. 32 (5) , pp. 869–78, 1996.
    • P. White, D. Squirrell, P. Arnaud, C. Lowe and J. Murray, “Improved thermostability of the North American firefly luciferase: saturation mutagenesis at position 354.”, The Biochemical journal, vol. 319 ( Pt 2) , pp. 343–50, 1996.