Role of polycomb/MLL-group genes in transcriptional control of target genes

Malek DJABALI


DR2
05 61 55 65 71

Team members

  Researcher
  • Maëlle CARRAZ
  Postdoc
  • Raphaël CULERRIER

Presentation

Our lab is interested in epigenetic gene regulation dictated by chromatin modifications. We examine the mechanism of stable inherited transcriptional repression by Polycomb-group (Pc-G)/MLL protein complexes, and the effects of deregulation of these genes on development, cell cycle control, and cancer formation. Studies on Pc-G/MLL have demonstrated that beside their function in controlling the expression of Hox genes, Pc-G/MLL play a central role in cell proliferation through the control of the INK4ab/ARF locus.


We focus on the regulation of the INK4b-ARF-INK4a tumour suppressor locus and its role in the achievement of cellular senescence, a permanent growth arrest directed by a wide range of stress. Senescence is view as a defence against oncogenic insults, and defines limits on the proliferative potential of stem and progenitor cell populations. In the course of tumourigenesis, an enrichment of senescent cells is often seen in pre-neoplastic lesions, (lung adenomas and other cancer). This observation together with the fact that mutations disabling senescence are required to cooperate in cancer progression and suggest that senescence constitutes a bona fide tumour suppressor mechanism.


Our current goal is to determine how different signalling pathways affect transcription of the locus by altering Polycomb/MLL binding at the Ink4/Arf locus and as a conscequence the state of histone modifications in the neighbouring chromatin.


We use knock out Polycomb/MLL mouse models to dissect the function between tumor suppression and aging

 

Publications

  • 2014 Jan Mishra BP, Zaffuto KM, Artinger EL, Org T, Mikkola HKA, Cheng C, Djabali M, Ernst P (2014) The histone methyltransferase activity of MLL1 is dispensable for hematopoiesis and leukemogenesis. Cell Reports in press
  • 2013 Jan Artinger E, Mishra B, Li B, Zaffuto K, Cheng C, Org T, Mikkola H, Djabali M, Ernst P (2013) MLL1-dependent pathways and mechanisms that maintain hematopoiesis. Exp Hematol 20:
  • 2013 Jan Djabali M (2013) MLL1 and menin: not partners in crime? Blood 122, 1995 Spec No 3:19-24
  • 2011 Jan Aranzazu Villasante, Daniela piazzolla, Han Li, Gonzalo Gomez, Malek Djabali and Manuel Serrano. Epigenetic regulation of Nanog expression by Ezh2 in pluripotent stem cells. Cell Cycle (2011)10:9, 1-11
  • 2009 Jan Agherbi H, Gaussmann A, Poulin L, Serrano M, Djabali M (2009) Polycomb mediated epigenetic silencing and replication timing at the INK4a/ARF locus during senescence. PLoS One 4:e5622

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Université Paul Sabatier
118 Route de Narbonne

31062 TOULOUSE Cedex
France

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