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Histone acetyltransferase activity of MOF is required for adult but not early fetal hematopoiesis in mice.
MOF 的组蛋白乙酰转移酶活性是小鼠成年但早期胎儿造血所必需的。

摘要

K(lysine) acetyltransferase 8 (KAT8, also known as MOF) mediates the acetylation of histone H4 at lysine 16 (H4K16ac) and is crucial for murine embryogenesis. Lysine acetyltransferases have been shown to regulate various stages of normal hematopoiesis. However, the function of MOF in hematopoietic stem cell (HSC) development has not yet been elucidated. We set out to study the role of MOF in general hematopoiesis by using a Vav1-cre-induced conditional murine Mof knockout system and found that MOF is critical for hematopoietic cell maintenance and HSC engraftment capacity in adult hematopoiesis. Rescue experiments with a MOF histone acetyltransferase domain mutant illustrated the requirement for MOF acetyltransferase activity in the clonogenic capacity of HSCs and progenitors. In stark contrast, fetal steady-state hematopoiesis at embryonic day (E) 14.5 was not affected by homozygous Mof deletion despite dramatic loss of global H4K16ac. Hematopoietic defects start manifesting in late gestation at E17.5. The discovery that MOF and its H4K16ac activity are required for adult but not early and midgestational hematopoiesis supports the notion that multiple chromatin regulators may be crucial for hematopoiesis at varying stages of development. MOF is therefore a developmental-stage-specific chromatin regulator found to be essential for adult but not early fetal hematopoiesis.

译文

K (赖氨酸) 乙酰转移酶 8 (KAT8,也称为 MOF) 介导组蛋白 H4 在赖氨酸 16 (H4K16ac) 处的乙酰化,对小鼠胚胎发生至关重要。赖氨酸乙酰转移酶已被证明可以调节正常造血的各个阶段。然而,MOF 在造血干细胞 (HSC) 发育中的功能尚未阐明。我们开始通过使用一种 Vav1-cre-induced 的条件性鼠 MOF 基因敲除系统来研究 Mof 在一般造血中的作用,并发现 MOF 对于造血细胞维持和成人造血中的 HSC 植入能力至关重要。MOF 组蛋白乙酰转移酶结构域突变的救援实验说明了 HSCs 和祖细胞克隆形成能力对 MOF 乙酰转移酶活性的要求。与之形成鲜明对比的是,尽管整体 H4K16ac 显著缺失,胚胎时期 (E) 14.5 的胎儿稳态造血并未受到纯合 Mof 缺失的影响。造血缺陷在妊娠晚期 e17.5 开始显现。MOF 及其 H4K16ac 活性是成人造血所必需的,但不是早期和中孕期造血,这一发现支持了多种染色质调节剂可能对不同发育阶段的造血至关重要的观点。因此,MOF 是一种发育阶段特异性染色质调节剂,被发现对成人造血至关重要,但对早期胎儿造血不重要。

Histone acetyltransferase

内分泌 临床研究术语
概述  :  

组蛋白乙酰转移酶(HATs)是通过将乙酰基从乙酰辅酶A转移形成ε-N-乙酰赖氨酸来乙酰化组蛋白中保守的赖氨酸氨基酸的酶。DNA包裹在组蛋白周围,通过将乙酰基转移到组蛋白上,可以打开和关闭基因。通常,组蛋白乙酰化增加基因表达,组蛋白乙酰化与转录激活有关,并与常染色质相关。常染色质的致密性较低,它使转录因子更容易与DNA的调节位点结合,从而引起转录激活。 催化机制 HATs催化的基本机理涉及乙酰基从乙酰辅酶A转移到组蛋白内目标赖氨酸侧链的ε-

histone   英 /'hɪstəʊn/  美 /'hɪston/

释    义   n. [生化] 组蛋白

例    句   Histones are proteins that regulate DNA packing, and histone deacetylases are enzymes that control the way those proteins work.组蛋白控制DNA折叠,而组蛋白去乙酰酶抑制剂是种控制这些蛋白质工作的酶。

 

acetyltransferase

释    义   乙酰转移酶,转乙酰酶

例    句   These help a mitochondrial enzyme called carnitine acetyltransferase to do its job.这两种分子有助于被称作肉碱乙酰转移酶的线粒体酶发挥作用。

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