Transcriptome-wide m6A profiles analysis in response to hypoxia

Recently, many studies have focused on the epigenetics such as histone modification and DNA methylation upon hypoxic stress. However, little is known about the the m6A epitranscriptome in response to hypoxia. In this study, we report that hypoxia systematically inhibit the m6A pathway through reducing the total m6A level and the expression of m6A readers. Deep m6A transcriptome sequencing revealed a drastic reprogramming of m6A epitranscriptome during cellular hypoxia. Integration m6A epitranscriptome with RNA-Seq or LC-MS/MS based proteome analysis of cells upon hypoxic stress revealed that the reprogramming of m6A epitranscriptome remodels the transcriptome and proteome to support the efficient generation of energy for adaption to hypoxia. Taken together, our studies indicated that the crosstalk between m6A and HIF1 pathway was essential for the cellular response to hypoxia, and provided profound insights into the molecular mechanism underlying the hypoxic responsive process. Overall design: meRIP-seq, RNA-seq for the human HeLa cervical cancer cells under the normoxia vs. hypoxia(6h, 12h, 24h, 1% oxygen) conditions