The selector gene Pax7 dictates alternate pituitary cell fates through its pioneer action on chromatin remodeling.
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.
Laboratoire de Génétique Moléculaire, Institut de Recherches Cliniques de Montréal (IRCM), Montréal, Quebec, Canada.
Lionel
L
Budry
Aurélio
A
Balsalobre
Yves
Y
Gauthier
Konstantin
K
Khetchoumian
Aurore
A
L'honoré
Sophie
S
Vallette
Thierry
T
Brue
Dominique
D
Figarella-Branger
Björn
B
Meij
Jacques
J
Drouin
D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D042002:Chromatin Assembly and Disassembly; D004285:Dogs; D006801:Humans; D051379:Mice; D051763:PAX7 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D047748:Pituitary ACTH Hypersecretion / Q000503:physiopathology; D010902:Pituitary Gland / Q000166:cytology* / Q000378:metabolism*
D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse