Argonaute proteins regulate a specific network of genes through KLF4 in mouse embryonic stem cells

• Main Authors: Ciaudo, C. (Author), Fäh, T. (Author), Hermes, V. (Author), Müller, M. (Author), Ngondo, R.P (Author), Peña-Hernández, R. (Author), Santoro, R. (Author), Schaefer, M. (Author), Spies, D. (Author)
• Format: Article
• Language: English
• Published: Cell Press 2022
• Subjects: Argonautes; CTCF; H3K27me3; integrative analysis; KLF4; PRC2
• Online Access: View Fulltext in Publisher

 The Argonaute proteins (AGOs) are well known for their role in post-transcriptional gene silencing in the microRNA (miRNA) pathway. Here we show that in mouse embryonic stem cells, AGO1&2 serve additional functions that go beyond the miRNA pathway. Through the combined deletion of both Agos, we identified a specific set of genes that are uniquely regulated by AGOs but not by the other miRNA biogenesis factors. Deletion of Ago2&1 caused a global reduction of the repressive histone mark H3K27me3 due to downregulation at protein levels of Polycomb repressive complex 2 components. By integrating chromatin accessibility, prediction of transcription factor binding sites, and chromatin immunoprecipitation sequencing data, we identified the pluripotency factor KLF4 as a key modulator of AGO1&2-regulated genes. Our findings revealed a novel axis of gene regulation that is mediated by noncanonical functions of AGO proteins that affect chromatin states and gene expression using mechanisms outside the miRNA pathway. © 2022 The Author(s)