Journal
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 411, Issue C, Pages 113-120Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2015.04.018
Keywords
Parathyroid hormone; Transcriptional regulation; Gata3; MafB; Gcm2; Hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome
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Funding
- Japan Society for the Promotion of Science (JSPS)
- JSPS
- Grants-in-Aid for Scientific Research [25461353, 25111720] Funding Source: KAKEN
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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 syndromeassociated Gata3 mutants were defective in activating the PTH promoter. These results suggest that Gata3 is a critical regulator of PTH gene expression. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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