FIAT represses ATF4-mediated transcription to regulate bone mass in transgenic mice.

Article Details

Citation

Yu VW, Ambartsoumian G, Verlinden L, Moir JM, Prud'homme J, Gauthier C, Roughley PJ, St-Arnaud R

FIAT represses ATF4-mediated transcription to regulate bone mass in transgenic mice.

J Cell Biol. 2005 May 23;169(4):591-601.

PubMed ID
15911876 [ View in PubMed
]
Abstract

We report the characterization of factor inhibiting activating transcription factor 4 (ATF4)-mediated transcription (FIAT), a leucine zipper nuclear protein. FIAT interacted with ATF4 to inhibit binding of ATF4 to DNA and block ATF4-mediated transcription of the osteocalcin gene in vitro. Transgenic mice overexpressing FIAT in osteoblasts also had reduced osteocalcin gene expression and decreased bone mineral density, bone volume, mineralized volume, trabecular thickness, trabecular number, and decreased rigidity of long bones. Mineral homeostasis, osteoclast number and activity, and osteoblast proliferation and apoptosis were unchanged in transgenics. Expression of osteoblastic differentiation markers was largely unaffected and type I collagen synthesis was unchanged. Mineral apposition rate was reduced in transgenic mice, suggesting that the lowered bone mass was due to a decline in osteoblast activity. This cell-autonomous decrease in osteoblast activity was confirmed by measuring reduced alkaline phosphatase activity and mineralization in primary osteoblast cultures. These results show that FIAT regulates bone mass accrual and establish FIAT as a novel transcriptional regulator of osteoblastic function.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Cyclic AMP-dependent transcription factor ATF-4P18848Details