Department of Life Science, University of Seoul, Seoul 02504, Korea.
BMB Rep. 2017 Nov;50(11):537-538. doi: 10.5483/bmbrep.2017.50.11.200.
Hypoxia affects various physiological and pathophyological processes. Hypoxia changes the expression of hypoxiaresponsive genes through two main pathways. First, hypoxia activates transcription factors (TF) such as Hypoxia-inducible Factor (HIF). Second, hypoxia decreases the activity of Jumonji C domain-containing histone demethylases (JMJDs) that require O2 and α-Ketoglutarate (α-KG) as substrates. The JMJDs affect gene expression through their regulation of active or repressive histone methylations. Profiling of H3K4me3, H3K9me3, and H3K27me3 under both normoxia and hypoxia identified 75 TFs whose binding motifs were significantly enriched in the methylated regions of the genes. TFs showing similar binding strengths to their target genes might be under the 'metabolic control' which changes histone methylation and gene expression by instant changing catalytic activities of resident histone demethylases. [BMB Reports 2017; 50(11): 537-538].
缺氧影响各种生理和病理生理过程。缺氧通过两种主要途径改变缺氧反应基因的表达。首先，缺氧激活转录因子（TF），如缺氧诱导因子（HIF）。其次，缺氧降低了需要氧气和α-酮戊二酸（α-KG）作为底物的 Jumonji C 结构域含有组蛋白去甲基酶（JMJDs）的活性。JMJDs 通过调节活性或抑制性组蛋白甲基化来影响基因表达。在常氧和缺氧条件下对 H3K4me3、H3K9me3 和 H3K27me3 进行分析，确定了 75 个 TF，其结合基序在基因的甲基化区域中显著富集。与靶基因具有相似结合强度的 TF 可能受到“代谢控制”的影响，通过即时改变驻留组蛋白去甲基酶的催化活性来改变组蛋白甲基化和基因表达。[BMB 报告 2017；50(11):537-538]。
