FUNCTIONAL GENOMICS OF IMPRINTED GENES
Department: Cancer biology - Research axis: Molecular & cellular networks

 

Research subject

Parental genomic imprinting is an epigenetic mechanism that restrains the expression of one allele of affected genes depending on its parental origin, paternal or maternal. Genomic imprinting targets about a hundred genes in placental mammals (eutherians), less than a dozen in marsupials (metatherians), and is not affecting egg-laying mammals (prototherians) and other clades (birds, reptiles, fishes...).

The alteration of genomic imprinting at defined loci results in different syndromes with complex phenotypes : Silver-Russel, Angelman, Prader-Willi, Beckwith-Wiedemann and TNDM (Transient Neonatal Diabetes Mellitus). In addition, a number of imprinted genes are involved in tumor formation as oncogenes or tumor suppressor genes.

The present research on genomic imprinting is focused on 3 main questions :

  • What selective advantage is given by the implementation of parental genomic imprinting during mammalian evolution, at the transition from prototherian to metatherian?
  • What molecular mechanisms are involved in differential marking of paternal and maternal alleles during gametogenesis? How do these marks lead to mono-allelic expression of the targeted genes?
  • What is special with respect to imprinted gene function that may explain why these genes were targeted by a specific mechanism of gene regulation?

Our group is addressing the latter question, and seeks to identify the molecular functions and the biological processes controlled by imprinted genes.

 

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Team

Team leader

Laurent Journot
DR2, CNRS


  IGF Sud 021

  04 34 35 92 41

 

Staff

Tristan Bouschet
CRCN, Inserm


  IGF Sud 022

  04 34 35 92 40

 

Ali Janbain
Doctorant(e), UM


  Fac de pharma

  04 11 75 97 36

 

Anne Le Digarcher
TCE, CNRS


  IGF Sud 022

  04 34 35 92 40

 

Jean Peyhardi
MCF, UM


  Fac de pharma

  04 11 75 97 36

 

Christelle Reynes
MCF, UM


  Fac de Pharma

  04 11 75 96 83

 

Robert Sabatier
PU, UM


  Fac de Pharma

  04 11 75 96 80

 

Annie Varrault
CRCN, CNRS


  IGF Sud 022

  04 34 35 92 40

 

Myrtille Vivien
MCF, UM


  Fac de Pharma

  04 11 75 96 82

 


Major publications

  • Varrault A, Eckardt S, Le Digarcher A, Sassetti I, Girard B, Meusnier C, Ripol C, Badalyan A, Bertaso F, McLaughlin J, Journot L, Bouschet T (2017) Mouse parthenogenetic embryonic stem cells with biparental-like expression of imprinted genes generate cortical-like neurons that integrate into the injured adult cerebral cortex. Stem Cells. in press
  • Varrault A, Dantec C, Le Digarcher A, Chotard L, Bilanges B, Parrinello H, Dubois E, Rialle S, Severac D, Bouschet T, Journot L (2017) Identification of Plagl1/Zac1 binding sites and target genes establishes its role in the regulation of extracellular matrix genes and the imprinted gene network. Nucleic Acids Res. 45:10466-80
  • Bouschet T, Dubois E, Reynès C, Kota S, Rialle S, Maupetit-Méhouas S, Pezet M, Le Digarcher A, Nidelet S, Demolombe V, Cavelier P, Meusnier C, Maurizy C, Sabatier R, Feil R, Arnaud P, Journot L, Varrault A (2017) In vitro corticogenesis from embryonic stem cells recapitulates the in vivo epigenetic control of imprinted gene expression. Cereb Cortex. 27:2418-33
  • Al Adhami H, Evano B, Le Digarcher A, Gueydan C, Dubois E, Parrinello H, Dantec C, Bouschet T, Varrault A, Journot L (2015) A systems-level approach to parental genomic imprinting: the imprinted gene network includes extracellular matrix genes and regulates cell cycle exit and differentiation. Genome Res 25:353-67
  • Seibt J, Armant O, Le Digarcher A, Castro D, Ramesh V, Journot L, Guillemot F, Vanderhaeghen P, Bouschet T (2012) Expression at the imprinted dlk1-gtl2 locus is regulated by proneural genes in the developing telencephalon. PLoS One 7:e48675
  • Gabory A, Ripoche MA, Le Digarcher A, Watrin F, Ziyyat A, Forné T, Jammes H, Ainscough J, Surani A, Journot L, Dandolo L (2009) The H19 gene acts as a trans regulator of the imprinted gene network controlling growth in mice. Development 36:3413-21
  • Varrault A, Gueydan C, Delalbre A, Bellmann A, Houssami S, Aknin C, Severac D, Chotard L, Kahli M, Le Digarcher A, Pavlidis P, Journot L (2006) Zac1 regulates an imprinted gene network critically involved in the control of embryonic growth. Dev Cell 11:711-22
  • Varrault A, Eckardt S, Le Digarcher A, Sassetti I, Girard B, Meusnier C, Ripol C, Badalyan A, Bertaso F, McLaughlin J, Journot L, Bouschet T (2017) Mouse parthenogenetic embryonic stem cells with biparental-like expression of imprinted genes generate cortical-like neurons that integrate into the injured adult cerebral cortex. Stem Cells. in press
 

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