PUBLICATION
Differential activation of pituitary hormone genes by human Lhx3 isoforms with distinct DNA binding properties
- Authors
- Sloop, K.W., Meier, B.C., Bridwell, J.L., Parker, G.E., Schiller, A.M., and Rhodes, S.J.
- ID
- ZDB-PUB-031024-1
- Date
- 1999
- Source
- Molecular endocrinology (Baltimore, Md.) 13(12): 2212-2225 (Journal)
- Registered Authors
- Rhodes, Sean
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Cell Line
- Cloning, Molecular
- DNA/metabolism*
- DNA, Complementary
- Escherichia coli/genetics
- Gene Expression*
- Homeodomain Proteins/genetics
- Homeodomain Proteins/metabolism*
- Homeodomain Proteins/pharmacology*
- Humans
- LIM-Homeodomain Proteins
- Mice
- Molecular Sequence Data
- Pituitary Gland/metabolism
- Pituitary Hormones/genetics*
- Promoter Regions, Genetic
- Recombinant Proteins
- Transcription Factors
- PubMed
- 10598593 Full text @ Mol. Endocrinol.
Citation
Sloop, K.W., Meier, B.C., Bridwell, J.L., Parker, G.E., Schiller, A.M., and Rhodes, S.J. (1999) Differential activation of pituitary hormone genes by human Lhx3 isoforms with distinct DNA binding properties. Molecular endocrinology (Baltimore, Md.). 13(12):2212-2225.
Abstract
Lhx3 is a LIM homeodomain transcription factor essential for pituitary development and motor neuron specification in mice. We identified two isoforms of human Lhx3, hLhx3a and hLhx3b, which differ in their ability to trans-activate pituitary gene targets. These factors are identical within the LIM domains and the homeodomain, but differ in their amino-terminal sequences preceding the LIM motifs. Both isoforms are localized to the nucleus and are expressed in the adult human pituitary, but gene activation studies demonstrate characteristic functional differences. Human Lhx3a trans-activated the alpha-glycoprotein subunit promoter and a reporter construct containing a high-affinity Lhx3 binding site more effectively than the hLhx3b isoform. In addition, hLhx3a synergized with the pituitary POU domain factor, Pit-1, to strongly induce transcription of the TSHbeta-subunit gene, while hLhx3b did not. We demonstrate that the differences in gene activation properties between hLhx3a and hLhx3b correlate with their DNA binding to sites within these genes. The short hLhx3b-specific amino-terminal domain inhibits DNA binding and gene
activation functions of the molecule. These data suggest that isoforms of Lhx3 may play distinct roles during development of the mammalian pituitary gland and other neuroendocrine systems.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping