Multi-dimensional histone modifications for coordinated regulation of gene expression under hypoxia or clioquinol (CQ) treatment.

Clioquinol (CQ) has been identified as a hypoxic mimicker to activate hypoxia-inducible factor-1α (HIF-1α) by inhibiting HIF-1a specific asparaginyl hypoxylase (Factor inhibiting HIF-1, FIH-1). We previously showed that hypoxia coordinately regulate induction or repression of hypoxia-responsive genes by altering different types of methylations (H3K4me3, H3K9me3, and H3K27me3) at gene level. Here, we investigated CQ-mediated regulation of the three histone methylations and whether CQ had a similar effect on histone methylation and transcription of target genes under hypoxia. To examine the genome-wide landscape of methylated histones affected by CQ, we performed ChIP-seq for H3K4me3, H3K9me3, and H3K27me3 in adipocyte-derived stem cells (hADSCs) under normoxia (N) and hypoxia (H) or with CQ treatment (CQ).