Abstract
Hepcidin (HAMP), an iron regulatory hormone synthesized by liver hepatocytes, works together with ferritin (FTH) and ferroportin (FPN) in regulating the storage, transport, and utilization of iron in the cell. Epigenetic mechanisms, especially acetylation, also play an important role in the regulation of iron metabolism. However, a target protein has not been mentioned yet. With this preliminary study, we investigated the effect of histone acetyltransferase TIP60 on the expression of HAMP, FTH, and FPN. In addition, how the depletion of Tip60, which regulates the circadian system, affects the daily expression of Hamp was examined at six Zeitgeber time (ZT) points. For this purpose, liver-specific Tip60 knockout mice (mutant) were produced with tamoxifen-inducible Cre/lox recombination and an iron overload model in mice was generated. While HAMP and FTH expressions decreased, FPN expression increased in the mutant group. Interestingly, there was no change in the iron content. A significant increase was observed in the expressions of HAMP, FTH, and FPN and total liver iron content in the liver tissue of the iron overload group. Since intracellular iron concentration is involved in regulating the circadian clock, temporal expression of Hamp was investigated in control and mutant groups at six ZT points. In the control group, Hamp accumulated in a circadian manner with maximal and minimal levels reaching around ZT16 and ZT8, respectively. In the mutant group, there was a significant reduction in Hamp expression in the light phase ZT0 and ZT4 and in the dark phase ZT16. These data are the first findings demonstrating a possible relationship between Tip60 and iron metabolism.
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The data supporting the findings of the present research are available on request from the corresponding author upon reasonable request.
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Acknowledgements
Conceived and designed the experiments: HB (group leader). Performed the experiments: NGB and MA. Analyzed the data: HB, NGB, ET, MA, and SK. Contributing reagents/materials/analysis tools: HB. Wrote the paper: HB, NGB, and ET. Financial support for the present research was received from the Scientific and Technological Research Council of Turkey (TUBITAK) [Grant Number: 114Z277] and Atatürk University Scientific Research Projects Coordination Commission [Grant Number: PRJ2013/79].
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Türkiye Bilimsel ve Teknolojik Araştirma Kurumu, 114Z277, Harun Budak,Atatürk Üniversitesi,PRJ2013/79, Harun Budak
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Baltacı, N.G., Toraman, E., Akyüz, M. et al. Tip60/Kat5 may be a novel candidate histone acetyltransferase for the regulation of liver iron localization via acetylation. Biometals 35, 1187–1197 (2022). https://doi.org/10.1007/s10534-022-00435-z
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DOI: https://doi.org/10.1007/s10534-022-00435-z