2026-02-27 東京科学大学
図. 本研究の概要図
＜関連情報＞
亜鉛欠乏時のKAT7依存性ヒストンH3K14アセチル化障害の病態生理学的意義 Pathophysiological significance of impaired KAT7-dependent histone H3K14 acetylation during zinc deficiency
Takao Fujisawa,Satoshi Takenaka,Lila Maekawa,Motoyuki Ogawa,Toshiyuki Kowada,Toshitaka Matsui,Shin Mizukami,Yugo Kato,Michio Suzuki,Hisashi Noma,Isao Naguro & Hidenori Ichijo
Nature Communications Published:17 February 2026
DOI:https://doi.org/10.1038/s41467-026-69476-z
Abstract
Zinc is an indispensable micronutrient for optimal physiological functions, and zinc deficiency has been implicated in the pathogenesis of various human diseases. One potential mechanism underlying such pathogenic effects is the alteration of gene expression caused by zinc deficiency; however, the details of this process remain largely unexplored. Here, we show that during zinc deficiency, the histone acetyltransferase KAT7 loses its enzymatic activity, leading to the attenuated acetylation of histone H3 at Lys14 (H3K14ac) at enhancer regions. Physiologically, the decrease in H3K14ac leads to the upregulation of the expression of ZIP10, a plasma membrane-localized zinc transporter, thereby facilitating the import of extracellular zinc to maintain cellular zinc homeostasis. Moreover, prolonged zinc deficiency in mice induced by a zinc-deficient diet or high-fat diet, accompanied by decreased H3K14ac levels in the liver, upregulated the expression of genes associated with intracellular lipid droplet formation, leading to the accumulation of lipids within liver tissue. Our findings demonstrate that cells respond to zinc deficiency by converting it into an epigenetic signal that drives physiological or pathophysiological biological processes.
