GENOME-WIDE ANALYSIS OF EPIGENETIC MODIFICATIONS UNDER HYPOXIC STRESS CONDITIONS

Abstract

Hypoxic stress is an important controller of cellular changes and is central to the development of different pathologies, such as cancer and ischemic illnesses. This paper examines genome-wide changes in the epigenetic state under hypoxia conditions and their effects on the regulation of genes. Hypoxia (1% O 2 24 h) was applied to human [cell line e.g., HeLa cells n 3 ) followed by integrated multi-omics analysis in the forms DNA methylation profiling (WGBS), histone modification analysis (ChIP-seq H3K27ac and H3K9me3), and transcriptomic profiling (RNA-seq ). Hypoxia caused a widespread epigenetic reprogramming and 3, 250 differentially methylated regions (DMRs) were found among which 1,870 were hyper methylated as well as 1,380 were hypo methylated (p < 0.01). The process of histone modification showed that the level of H3K27ac enrichment at promoter regions was 2.3-fold and that the redistribution of H3K9me3 across heterochromatin domains was 1.8-fold (p < 0.001). Transcriptomic revealed 1,120 up and 890 down regulated genes and VEGF, GLUT1 and CA9 among the key hypoxia-responsive genes some of which were upregulated by 2.54.2 with a p value of less than 0.001. Combined multi-omics analysis showed that there is a close association between angiogenesis, metabolic adaptation and cell survival regulation networks dominated by HIF-1 alpha and positioned between epigenetic change and gene expression (r = 0.76). All of this confirms that hypoxia promotes orchestrated genome-wide epigenetic rearrangement which offers an innovative gap in insights into transcriptional regulation as well as the prospective establishment of epigenetic biomarkers and therapeutic targets in hypoxia-linked illnesses.