Integrative CUT&Tag-RNA-Seq analysis of histone variant macroH2A1-dependent orchestration of human induced pluripotent stem cell reprogramming

Aim:Human induced pluripotent stem cells (iPSCs) are inefficiently derived from somatic cells by overexpression of defined transcription factors. Overexpression of H2A histone variant macroH2A1.1, but not macroH2A1.2, leads to increased iPSC reprogramming by unclear mechanisms. Materials & methods:Cleavage under targets and tagmentation (CUT&Tag) allows robust epigenomic profiling of a low cell number. We performed an integrative CUT&Tag-RNA-Seq analysis of macroH2A1-dependent orchestration of iPSCs reprogramming using human endothelial cells. Results:We demonstrate wider genome occupancy, predicted transcription factors binding, and gene expression regulated by macroH2A1.1 during reprogramming, compared to macroH2A1.2. MacroH2A1.1, previously associated with neurodegenerative pathologies, specifically activated ectoderm/neural processes. Conclusion:CUT&Tag and RNA-Seq data integration is a powerful tool to investigate the epigenetic mechanisms occurring during cell reprogramming.

Automated summary

This study used a combination of CUT&Tag and RNA-Seq data to analyze the differences between macroH2A1.1 and macroH2A1.2 during iPSCs reprogramming. The results demonstrated that macroH2A1.1 had wider genome occupancy and specifically activated ectoderm/neural processes during reprogramming.