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Hypoxia suffocates histone demethylases to change gene expression: a metabolic control of histone methylation
Hyunsung Park1,*
1Department of Life Science, University of Seoul, Seoul, 130-743, Republic of Korea
Hypoxia affects various physiological and pathophyological processes. Hypoxia changes the expression of the hypoxia-responsive 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 メ-Ketoglutarate (メ-KG) as substrates. The JMJDs affect gene expression through their regulation of the active or repressive histone methylations. We conducted profiling of H3K4me3, H3K9me3, and H3K27me3 under both normoxia and hypoxia identified 75 TFs, whose binding motifs were significantly (P<0.05) enriched in the methylated regions of the genes. Genes which the predicted TFs constantly bind but of which histone methylations are changed by hypoxia might be under the ‘metabolic control’. Under metabolic control, hypoxia instantly increases their histone methylation and gene expression not by changing the TF binding but by inhibiting catalytic activities of the resident histone demethylases.
Abstract, Accepted Manuscript(in press) [Submitted on October 23, 2017, Accepted on October 23, 2017]
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