Argonaute proteins regulate a specific network of genes through KLF4 in mouse embryonic stem cells
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Date
2022-05-10
Publication Type
Journal Article
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Abstract
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.
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published
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Journal / series
Volume
17 (5)
Pages / Article No.
1070 - 1080
Publisher
Elsevier
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Subject
Argonautes; KLF4; CTCF; H3K27me3; PRC2; integrative analysis
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Funding
173120 - Canonical and non-canonical functions of RNA interference proteins during mouse early development (SNF)
196861 - Unravelling (non)canonical functions of RNA interference factors during early mouse development (SNF)
182880 - NCCR RNA#38;Disease (51NF40-182880): Flexibility Grant (SNF)
196861 - Unravelling (non)canonical functions of RNA interference factors during early mouse development (SNF)
182880 - NCCR RNA#38;Disease (51NF40-182880): Flexibility Grant (SNF)