Gata3 cooperates with Gcm2 and MafB to activate parathyroid hormone gene expression by interacting with SP1.

Abstract

Haploinsufficiency of the Gata3 gene, which encodes a zinc-finger transcription factor, is associated with the disorder hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome in humans. However, the roles of Gata3 in transcriptional regulation in the parathyroid glands are not well-understood. In this study, we show that Gata3 activates transcription of parathyroid hormone (PTH), which is secreted from parathyroid glands and is critical for regulating serum calcium and phosphate homeostasis. Gata3 interacted with Gcm2 and MafB, two known transcriptional regulators of parathyroid development, and synergistically stimulated the PTH promoter. An SP1-binding element (GC box) located within the PTH-promoter proximal region was critical for activating transcription by Gata3. In addition, the ubiquitous transcription factor SP1 also interacted with Gata3 as well as MafB and Gcm2, and HDR syndrome-associated Gata3 mutants were defective in activating the PTH promoter. These results suggest that Gata3 is a critical regulator of PTH gene expression.

• Authors: Song-Iee Han, Yukino Tsunekage, Kohsuke Kataoka
• Journal: Molecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 411 Pg. 113-20 (Aug 15 2015) ISSN: 1872-8057 [Electronic] Ireland
• PMID: 25917456 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• GATA3 Transcription Factor
• GATA3 protein, human
• GCM2 protein, human
• MAFB protein, human
• MafB Transcription Factor
• Nuclear Proteins
• Parathyroid Hormone
• Sp1 Transcription Factor
• Sp1 protein, human
• Transcription Factors

Topics

• Animals
• Cell Line
• Deafness (genetics, metabolism)
• GATA3 Transcription Factor (metabolism)
• Gene Expression Regulation
• HeLa Cells
• Humans
• Hypoparathyroidism (genetics, metabolism)
• Kidney Diseases (genetics, metabolism)
• MafB Transcription Factor (metabolism)
• Mesocricetus
• Nuclear Proteins (metabolism)
• Parathyroid Hormone (genetics, metabolism)
• Promoter Regions, Genetic
• Sp1 Transcription Factor (metabolism)
• Syndrome
• Transcription Factors (metabolism)