Argonaute Proteins Regulate a Specific Network of Genes Through KLF4 in Mouse Embryonic Stem Cells

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2022 Apr 22

PMID 35452597

Authors

Madlen Muller

Moritz Schaefer

Tara Fah

Daniel Spies

Victoria Hermes

Richard Patryk Ngondo

Rodrigo Pena-Hernandez

Raffaella Santoro

Constance Ciaudo

Affiliations

Soon will be listed here.

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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