Genome-wide R-loop landscapes during epigenetic programming and reprogramming
收藏干细胞与再生医学数据中心2022-02-20 更新2024-03-06 收录
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The role of R-loops, three-stranded nucleic acid structures harboring DNA:RNA hybrids, in regulating cell fate decisions remains elusive. Using an isogenic human stem cell platform, we systematically characterized R-loops, DNA methylation, histone modifications, and chromatin accessibility in pluripotent cells and their lineage-differentiated derivatives. We found that R-loops initially formed co-transcriptionally at pluripotency genes in pluripotent cells. Upon differentiation into neural, mesenchymal, endothelial, and smooth muscle lineages, R-loops and repressive chromatin marks increased synergistically on pluripotency genes and undesired lineage genes, while new R-loops formed co-transcriptionally to activate lineage determination genes. In reprogrammed pluripotent cells, features of epigenetic memory and aberrant gene expression were initially present in regions highly enriched with R-loops, but became resolved with serial passaging. Our analysis defines a multi-faceted role of R-loops in cell fate determination and adds an additional layer of epigenetic control of cell state changes and cell fate memory.
提供机构：
State Key Laboratory of Stem Cell and Reproductive Biology
创建时间：
2022-02-20
