The selector gene Pax7 dictates alternate pituitary cell fates through its pioneer action on chromatin remodeling.
Genes Dev
; 26(20): 2299-310, 2012 Oct 15.
Article
in En
| MEDLINE
| ID: mdl-23070814
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pituitary Gland
/
Cell Differentiation
/
Chromatin Assembly and Disassembly
/
PAX7 Transcription Factor
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Genes Dev
Journal subject:
BIOLOGIA MOLECULAR
Year:
2012
Document type:
Article
Affiliation country:
Canada
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA