Hypoxia suffocates histone demethylases to change gene expression: a metabolic control of histone methylation

缺氧抑制组蛋白去甲基化酶活性,从而改变基因表达:组蛋白甲基化的代谢调控

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Abstract

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].

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