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Biochem Biophys Rep. 2016 Oct 15;8:340-345. doi: 10.1016/j.bbrep.2016.10.007. eCollection 2016 Dec.

Role of MIZ-1 in AMELX gene expression.

Author information

1
Brain Korea 21 Plus Project for Medical Science, Department of Biochemistry and Molecular Biology, Severance Biomedical Research Institute, Yonsei University School of Medicine, 134 ShinChon-Dong, SeoDaeMoon-Ku, Seoul 120-752, Korea.
2
Kanagawa Dental University, 82 Inaooka-Chou, Yokosuka-Shikanagawa-Ken, Japan.
3
The Center for Craniofacial Molecular Biology, The Herman Ostrow School of Dentistry of the University of Southern California, Los Angeles, CA, USA.

Abstract

Amelogenin (AMELX) is the main component of the developing tooth enamel matrix and is essential for enamel thickness and structure. However, little is known about its transcriptional regulation. Using gene expression analysis, we found that MIZ-1, a potent transcriptional activator of CDKN1A, is expressed during odontoblastic differentiation of hDPSCs (human dental pulp stem cells), and is essential for odontoblast differentiation and mineralization. We also investigated how MIZ-1 regulates gene expression of AMELX. Oligonucleotide-pull down assays showed that MIZ-1 binds to an MRE (MIZ-1 binding element) of the AMELX proximal promoter region (bp, -170 to -25). Combined, our ChIP, transient transcription assays, and promoter mutagenesis revealed that MIZ-1 directly binds to the MRE of the Amelx promoter recruits p300 and induces Amelx gene transcription. Finally, we show that the zinc finger protein MIZ-1 is an essential transcriptional activator of Amelx, which is critical in odontogenesis and matrix mineralization in the developing tooth.

KEYWORDS:

Amelx; MIZ-1; Odontoblast differentiation; Odontoblast mineralization

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