缺氧环境下HIF-1α与H3K4的相互作用

The interaction between HIF-1αand H3K4 in hypoxic environment

地球上的大多数生物依赖氧气来维持机体代谢内稳态,这个过程往往需要缺氧诱导因子‐1α(hypoxia inducible factor‐1α,HIF‐1α)对氧气变化的感知和应答。随着研究的不断深入,缺氧状态下的组蛋白修饰和基因调控分子机制逐渐清晰,其中,组蛋白H3赖氨酸K4(histone 3 lysine 4,H3K4)作为基因转录激活的重要组蛋白修饰位点受到越来越多的关注。缺氧环境下,HIF‐1α与H3K4变化趋势一致,H3K4去乙酰化修饰能控制HIF‐1α的稳定性,而部分H3K4去甲基化酶可能是HIF‐1α的直接作用靶点,且HIF‐1α可募集H3K4甲基转移酶共同激活相应靶基因。本综述探讨HIF‐1α与H3K4之间的相互作用关系,以更详细地了解HIF-1α应对缺氧环境时复杂的生物学过程。

Most organisms on earth rely on oxygen to maintain metabolic homeostasis,which typically relies on hypoxia inducible factor-1α(HIF-1α).The function of HIF-1αis to perceive and respond to changes in oxygen.With the continuous deepening of research,the molecular mechanisms of histone modification and gene regulation under hypoxic conditions are gradually becoming clear.Among them,histone 3 lysine 4(H3K4),as an important histone modification site for gene transcription activation,has received increasing attention.Under hypoxic conditions,HIF-1αis consistent with the trend of H3K4 changes,H3K4 deacetylation modification can control HIF-1αstability performance,thus some H3K4 demethylases may be HIF-1αdirect target of action and HIF-1αcan recruit H3K4 methyltransferase to jointly activate corresponding target gene.For a more detailed understanding of HIF-1αin the complex biological process of hypoxic environment,we investigate the correlations between HIF-1αand H3K4.