Gata3 cooperates with Gcm2 and MafB to activate parathyroid hormone gene expression by interacting with SP1.
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.
Laboratory of Molecular Medical Bioscience, Graduate School of Medical Life Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
Song-Iee
SI
Han
Laboratory of Molecular Medical Bioscience, Graduate School of Medical Life Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
Yukino
Y
Tsunekage
Laboratory of Molecular Medical Bioscience, Graduate School of Medical Life Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan. Electronic address: kkataoka@tsurumi.yokohama-cu.ac.jp.
Kohsuke
K
Kataoka
D000818:Animals; D002460:Cell Line; D003638:Deafness / Q000235:genetics / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000378:metabolism*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D007011:Hypoparathyroidism / Q000235:genetics / Q000378:metabolism; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism; D051258:MafB Transcription Factor / Q000378:metabolism*; D008647:Mesocricetus; D009687:Nuclear Proteins / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D013577:Syndrome; D014157:Transcription Factors / Q000378:metabolism*
D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C119532:GCM2 protein, human; C490407:MAFB protein, human; D051258:MafB Transcription Factor; D009687:Nuclear Proteins; D010281:Parathyroid Hormone; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; D014157:Transcription Factors
Gata3; Gcm2; Hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome; MafB; Parathyroid hormone; Transcriptional regulation