Simon AMIARD

Chargé de Recherche
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AccueilSimon AMIARD
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AMIARD
Simon
Chargé de Recherche
CR

Présentation

During my career, I have explored the roles of various proteins involved in telomere protection, DNA repair, chromatin structure and gene expression, mainly using Arabidopsis thaliana as a model organism.
During my PhD (2003–2007), I investigated the role of the TRF2 protein in human telomere folding and protection. My work demonstrated how telomeres fold back on themselves to prevent DNA ends from being recognized as double-strand breaks (Amiard, 2007). This research provided critical insights into telomere biology and genome stability.
As a postdoctoral researcher (2008–2012) in Charles White's team at the GReD institute in Clermont-Ferrand, I shifted my focus to Arabidopsis thaliana, studying how this model plant recognizes and repairs double-strand DNA breaks caused by genotoxic agents or unprotected telomeres (Amiard, 2010–2014).
In 2012, I was recruited to the CNRS to lead a project aimed at identifying proteins responsible for telomere protection in Arabidopsis thaliana. This work led to the discovery of several proteins that specifically recognize double-stranded telomeric sequences, including seven proteins containing GH1 domains. These findings laid the foundation for my current research which is dedicated to understanding the molecular mechanisms underlying chromatin organisation and transcriptional regulation, with a particular focus on GH1-domain proteins in plants.

CNRS researcher, iGRED, Team Probst-Tatout, since 2018

CNRS researcher, iGRED, Team C. White, 2012-2018
Post-doctorant, iGRED, Clercmont-Ferrand, Team C. White, 2008-2012
Ph.D, ENS Lyon, 2003-07, Team E. Gilson

Recherche

Understanding the Role of GH1 Domain Proteins in Chromatin Organization and Gene Regulation

My current research focuses on three families of GH1 domain proteins: Linker histone H1, High Mobility Group A (GH1-HMGA) and Telomere Repeat Binding (GH1-TRB):

Nucleosomes interact with the globular domain (GH1) of linker histone H1, which plays a crucial role in chromatin compaction. In addition to H1, plants have two unique families of proteins containing the GH1 domain: GH1-HMGA (high mobility group A) proteins and TRB (telomere repeat binding) proteins. GH1-HMGA proteins are characterised by their AT-hook domains that recognise the AT-rich region, whereas TRB proteins have a Myb DNA-binding domain that allows interaction with telomeric sequences. We are studying how these GH1 domain-containing proteins either cooperate or compete for chromatin binding sites influencing processes such as chromatin structure maintenance and gene expression modulation.

Key Findings

Our work participates in the understanding on the function of the five TRB proteins (TRB1-5), which recognize the telobox DNA-binding motif present at telomeres, but also at thousands of promoters. At some of these promoters, TRB1, TRB2, and TRB3 proteins recruit the Polycomb group complex 2 (PRC2) to deposit H3K27me3 and JMJ14 to remove H3K4me3, thus repressing transcription at these loci. We contributed to show that H1 histones prevent TRB1-3 binding to telobox-rich interstitial telomere repeats (ITRs) (Teano, 2023).

We are specifically interesting to elucidate the function of TRB4 and TRB5, two related paralogues forming a distinct TRB clade. In contrast to TRB1, 2, and 3, the absence of these two proteins does not affect the levels of H3K4me3 or H3K27me3 suggesting a different mode of action. Our results indicate an antagonism between the two clades, as combining clade I mutants with a prc2 mutant exacerbate prc2 phenotypes, while clade II mutants compensate prc2 defects. Transcriptomic studies revealed that gene upregulation in the prc2 mutant requires TRB4 and TRB5, particularly at MADS-Box genes like SOC1 and SEPs, which are essential for correct plant development and require fine-tuned transcriptional regulation, revealing the unexpected function of TRB4 and TRB5 as transcriptional activators (Amiard, 2024).

Research Directions: Role of GH1 domain proteins in genome regulation and coordinating Polycomb activity

Our aim is to dissect the role of Telomere Repeat Binding (TRB) proteins, GH1-High mobility group proteins (GH1-HMGA) and the linker histone H1 in regulating Polycomb activity. To explain the surprising observation that TRB4 and 5, in contrast to TRB1, 2 and 3, act as transcriptional activators of PRC2-controlled genes, we have screened an EMS-mutagenized population of trb45 mutants for enhancer or suppressor phenotypes. This screen resulted in several promising suppressor mutants, that will help us to dissect mechanistically how TRB4 and TRB5 regulate gene expression.

To study GH1-HMGA proteins, we have developed specific antibodies against GH1-HMGA1/2 to map their genome-wide distribution in wild type and mutant background for histone H1 and TRB proteins, probing competitive or synergistic binding among GH1-domain proteins. Our studies on GH1-HMGAs have revealed their specific binding to transposable elements (TEs) and their altered chromatin enrichment profiles in the absence of histone H1. These findings suggest a potential role in regulating TEs and chromatin dynamics.

Finally, in collaboration with the company LUMICKS (Netherlands) and the team of G. Farge (UCA), we are developing single molecule approaches to investigate the competitive interactions and DNA binding dynamics of GH1 proteins at the single molecule level and exploring their biochemical properties using advanced single-molecule techniques.

Methodologies

To unravel the mechanisms of action for these proteins, we employ a multidisciplinary approach: genetics, proteomics, epigenomics and biophysics.

Funding

ANR EpiLinks, I-site Emergence GH1-domain.

People

Emmanuel Vanrobays (MCU-UCA)

Sylvie Tutois (MCU-UCA)

Léa Feit (PhD student – CNRS)

Hafsa El Idrissi Mboutassim (PhD student – UCA)

Collaborators

  1. Barnèche (IBPS, Paris)
  2. Quadrana (IPS2, Paris)
  3. Farge (UCA), Clermont-Ferrand)
  4. Lorković (GMI, Vienna)
  5. Bischoff (UZH, Zurich)
  6. Carles (CEA, Grenoble)

Publications

23 publications
2021

Polycomb-dependent differential chromatin compartmentalization determines gene coregulation in Arabidopsis.

Publié le 03 Juin 2021 dans Genome research , vol. 31 - pp 1230-44

Huang Y, Sicar S, Ramirez-Prado JS, Manza-Mianza D, Antunez-Sanchez J, Brik-Chaouche R, Rodriguez-Granados NY, An J, Bergounioux C, Mahfouz MM, Hirt H, Crespi M, Concia L, Barneche F, Amiard S , Probst AV , Gutierrez-Marcos J, Ariel F, Raynaud C, Latrasse D, Benhamed M

2018

RAD51 and RTEL1 compensate telomere loss in the absence of telomerase.

Publié le 16 Mar 2018 dans Nucleic acids research , vol. 46 - pp 2432-2445

Olivier M , Charbonnel C , Amiard S , White CI , Gallego ME

The Linker Histone GH1-HMGA1 Is Involved in Telomere Stability and DNA Damage Repair.

Publié le 30 Mai 2018 dans Plant physiology , vol. 177 - pp 311-327

Charbonnel C , Rymarenko O, Da Ines O , Benyahya F, White CI , Butter F, Amiard S

2015

Highly efficient radiosensitization of human glioblastoma and lung cancer cells by a G-quadruplex DNA binding compound.

Publié le 06 Nov 2015 dans Scientific reports , vol. 5 - pp 16255

Merle P, Gueugneau M, Teulade-Fichou MP, Müller-Barthélémy M, Amiard S , Chautard E, Guetta C, Dedieu V, Communal Y, Mergny JL, Gallego M , White C , Verrelle P, Tchirkov A

Homology-dependent repair is involved in 45S rDNA loss in plant CAF-1 mutants.

Publié le 30 Jan 2015 dans The Plant journal : for cell and molecular biology , vol. 81 - pp 198-209

Muchová V, Amiard S , Mozgová I, Dvořáčková M, Gallego ME, White C , Fajkus J

2014

Responses to telomere erosion in plants.

Publié le 01 Mar 2014 dans PloS one , vol. 9 - pp e86220

Amiard S , Da Ines O , Gallego ME , White CI

Arabidopsis thaliana RNase H2 deficiency counteracts the needs for the WEE1 checkpoint kinase but triggers genome instability.

Publié le 30 Sep 2014 dans The Plant cell , vol. 26 - pp 3680-92

Kalhorzadeh P, Hu Z, Cools T, Amiard S , Willing EM, De Winne N, Gevaert K, De Jaeger G, Schneeberger K, White CI , De Veylder L

2012

A role for small RNAs in DNA double-strand break repair.

Publié le 30 Mar 2012 dans Cell , vol. 149 - pp 101-12

Wei W, Ba Z, Gao M, Wu Y, Ma Y, Amiard S , White CI , Rendtlew Danielsen JM, Yang YG, Qi Y

The N-terminal domains of TRF1 and TRF2 regulate their ability to condense telomeric DNA.

Publié le 30 Mar 2012 dans Nucleic acids research , vol. 40 - pp 2566-76

Poulet A, Pisano S, Faivre-Moskalenko C, Pei B, Tauran Y, Haftek-Terreau Z, Brunet F, Le Bihan YV, Ledu MH, Montel F, Hugo N, Amiard S , Argoul F, Chaboud A, Gilson E, Giraud-Panis MJ

2011

Recombination proteins and telomere stability in plants.

Publié le 30 Mar 2011 dans Current protein & peptide science , vol. 12 - pp 84-92

Amiard S , White C , Gallego ME

2010

Platination of telomeric DNA by cisplatin disrupts recognition by TRF2 and TRF1.

Publié le 30 Juin 2010 dans Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry , vol. 15 - pp 641-54

Ourliac-Garnier I, Poulet A, Charif R, Amiard S , Magdinier F, Rezaï K, Gilson E, Giraud-Panis MJ, Bombard S

TRF2 and apollo cooperate with topoisomerase 2alpha to protect human telomeres from replicative damage.

Publié le 23 Juil 2010 dans Cell , vol. 142 - pp 230-42

Ye J, Lenain C, Bauwens S, Rizzo A, Saint-Léger A, Poulet A, Benarroch D, Magdinier F, Morere J, Amiard S , Verhoeyen E, Britton S, Calsou P, Salles B, Bizard A, Nadal M, Salvati E, Sabatier L, Wu Y, Biroccio A, Londoño-Vallejo A, Giraud-Panis MJ, Gilson E

2009

TRF2 promotes, remodels and protects telomeric Holliday junctions.

Publié le 18 Mar 2009 dans The EMBO journal , vol. 28 - pp 641-51

Poulet A, Buisson R, Faivre-Moskalenko C, Koelblen M, Amiard S , Montel F, Cuesta-Lopez S, Bornet O, Guerlesquin F, Godet T, Moukhtar J, Argoul F, Déclais AC, Lilley DM, Ip SC, West SC, Gilson E, Giraud-Panis MJ

2007

A topological mechanism for TRF2-enhanced strand invasion.

Publié le 02 Mar 2007 dans Nature structural & molecular biology , vol. 14 - pp 147-54

Amiard S , Doudeau M, Pinte S, Poulet A , Lenain C, Faivre-Moskalenko C, Angelov D, Hug N, Vindigni A, Bouvet P, Paoletti J, Gilson E, Giraud-Panis MJ

2006

The Apollo 5′ exonuclease functions together with TRF2 to protect telomeres from DNA repair.

Publié le 11 Juil 2006 dans Current biology : CB , vol. 16 - pp 1303-10

Lenain C, Bauwens S, Amiard S , Brunori M, Giraud-Panis MJ, Gilson E

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Simon AMIARD

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