Temporal regulation of a paired-like homeodomain repressor/TLE corepressor complex and a related activator is required for pituitary organogenesis

Dasen, J. S., Martinez Barbera, J. P., Herman, T. S., Connell, S. O., Olson, L., Ju, B., Tollkuhn, J., Baek, S. H., Rose, D. W., Rosenfeld, M. G. (December 2001) Temporal regulation of a paired-like homeodomain repressor/TLE corepressor complex and a related activator is required for pituitary organogenesis. Genes Dev, 15 (23). pp. 3193-207. ISSN 0890-9369 (Print)0890-9369 (Linking)

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URL: http://www.ncbi.nlm.nih.gov/pubmed/11731482
DOI: 10.1101/gad.932601


Understanding the functional significance of the coordinate expression of specific corepressors and DNA-binding transcription factors remains a critical question in mammalian development. During the development of the pituitary gland, two highly related paired-like homeodomain factors, a repressor, Hesx1/Rpx and an activator, Prop-1, are expressed in sequential, overlapping temporal patterns. Here we show that while the repressive actions of Hesx1/Rpx may be required for initial pituitary organ commitment, progression beyond the appearance of the first pituitary (POMC) lineage requires both loss of Hesx1 expression and the actions of Prop-1. Although Hesx1 recruits both the Groucho-related corepressor TLE1 and the N-CoR/Sin3/HDAC complex on distinct domains, the repressor functions of Hesx1 in vivo prove to require the specific recruitment of TLE1, which exhibits a spatial and temporal pattern of coexpression during pituitary organogenesis. Furthermore, Hesx1-mediated repression coordinates a negative feedback loop with FGF8/FGF10 signaling in the ventral diencephalon, required to prevent induction of multiple pituitary glands from oral ectoderm. Our data suggest that the opposing actions of two structurally-related DNA-binding paired-like homeodomain transcription factors, binding to similar cognate elements, coordinate pituitary organogenesis by reciprocally repressing and activating target genes in a temporally specific fashion, on the basis of the actions of a critical, coexpressed TLE corepressor.

Item Type: Paper
Uncontrolled Keywords: Animals Basic Helix-Loop-Helix Transcription Factors Blotting, Western Cell Lineage Co-Repressor Proteins Embryonic and Fetal Development/ genetics Evolution, Molecular Feedback, Physiological Fibroblast Growth Factors/metabolism Gene Expression Regulation, Developmental HeLa Cells Homeodomain Proteins/chemistry/genetics/ metabolism Humans In Situ Hybridization Macromolecular Substances Mice Mice, Transgenic Models, Biological Mutation/genetics Nuclear Proteins/genetics/metabolism Pituitary Gland/cytology/ embryology/metabolism Precipitin Tests Protein Binding Protein Structure, Tertiary Repressor Proteins/chemistry/genetics/ metabolism Trans-Activators/chemistry/genetics/ metabolism
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > homeodomain protein
organs, tissues, organelles, cell types and functions > tissues types and functions > pituitary gland
CSHL Authors:
Communities: CSHL labs > Tollkuhn lab
Depositing User: Matt Covey
Date: 1 December 2001
Date Deposited: 23 Jul 2015 19:10
Last Modified: 23 Jul 2015 19:10
PMCID: PMC312840
Related URLs:
URI: https://repository.cshl.edu/id/eprint/31662

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