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Article Dans Une Revue Genes and Development Année : 2012

The selector gene Pax7 dictates alternate pituitary cell fates through its pioneer action on chromatin remodeling

Lionel Budry
  • Fonction : Auteur
Aurelio Balsalobre
  • Fonction : Auteur
Yves Gauthier
  • Fonction : Auteur
Konstantin Khetchoumian
  • Fonction : Auteur
Aurore L'Honore
  • Fonction : Auteur
Sophie Vallette
  • Fonction : Auteur
Thierry Brue
Bjorn Meij
  • Fonction : Auteur
Jacques Drouin
  • Fonction : Auteur

Résumé

The anterior and intermediate lobes of the pituitary gland derive from the surface ectoderm. They provide a simple system to assess mechanisms of developmental identity established by tissue determinants. Each lobe contains a lineage expressing the hormone precursor pro-opiomelanocortin (POMC): the corticotropes and melanotropes. The T-box transcription factor Tpit controls terminal differentiation of both lineages. We now report on the unique role of Pax7 as a selector of intermediate lobe and melanotrope identity. Inactivation of the Pax7 gene results in loss of melanotrope gene expression and derepression of corticotrope genes. Pax7 acts by remodeling chromatin and allowing Tpit binding to a new subset of enhancers for activation of melanotrope-specific genes. Thus, the selector function of Pax7 is exerted through pioneer transcription factor activity. Genome-wide, the Pax7 pioneer activity is preferentially associated with composite binding sites that include paired and homeodomain motifs. Pax7 expression is conserved in human and dog melanotropes and defines two subtypes of pituitary adenomas causing Cushing's disease. In summary, expression of Pax7 provides a unique tissue identity to the pituitary intermediate lobe that alters Tpit-driven differentiation through pioneer and classical transcription factor activities.

Dates et versions

hal-01544071 , version 1 (21-06-2017)

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Citer

Lionel Budry, Aurelio Balsalobre, Yves Gauthier, Konstantin Khetchoumian, Aurore L'Honore, et al.. The selector gene Pax7 dictates alternate pituitary cell fates through its pioneer action on chromatin remodeling. Genes and Development, 2012, 26 (20), pp.2299-2310. ⟨10.1101/gad.200436.112⟩. ⟨hal-01544071⟩
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