Herein, by combining previously published data and our findings, we have constructed a working model for epigenetic regulation of the HIF-1α at transcription level in breast cancer (Fig. 8f), and proposed that the coordinated effects of lower methylation frequencies at non-CpG/CpG sites and enhanced H3K9ac modification contribute to maintain the higher HIF-1α expression levels, particularly in breast cancer cells and tissue sample with highly malignant behaviors. Here, HIF1A is linked to breast cancer.