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Histone variant macroH2A1.1 enhances non-homologous end joining-dependent DNA double-strand-break repair and reprogramming efficiency of human iPSC

ABSTRACT: Here we used RNA-Seq to gain deep mechanistic insight into the effects of macroH2A1 splicing isoforms macroH2A1.1 and macroH2A1.2 on Human Umbelical Vein Endothelial Cells (HUVEC) undergoing cell reprogramming. The process was triggered using an episome construct carrying the reprogramming factors Oct4, Sox2, Klf4, L-Myc and Lin28. RNA-seq analysis was performed on the fourth day of the reprogramming process, to investigate the role. Heatmap anlysis of top 44 differently expressed genes (DEG) revealed that macroH2A1.1, but not macroH2A1.2,increased the expression of genes involved in DNA repair response (DDR) and cell reprogramming in HUVEC. Genes exhibiting absolute fold-change values >2 and p-values <0.05 were considered differentially expressed between contrasts. Statistical differences in gene expression were assessed by the ANOVA test. Correction for multiple test was achieved by the Benjamini-Hochberg procedure. The significance threshold was set to 0.05. Ingenuity pathway analysis (IPA) identified differences in evaluating top 44 DEG involved in DDR and top 12 DEG involved in cell reprogramming showed that macroH2A1.1 verexpression enhances several pathways involved in DNa repair and acquisition of cell pluripotency.

ORGANISM(S): Homo sapiens

PROVIDER: GSE164396 | GEO | 2021/01/08

REPOSITORIES: GEO

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