TY - JOUR T1 - AGO1 regulates pericentromeric regions in mouse embryonic stem cells JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202101277 VL - 5 IS - 6 SP - e202101277 AU - Madlen Müller AU - Tara Fäh AU - Moritz Schaefer AU - Victoria Hermes AU - Janina Luitz AU - Patrick Stalder AU - Rajika Arora AU - Richard Patryk Ngondo AU - Constance Ciaudo Y1 - 2022/06/01 UR - https://www.life-science-alliance.org/content/5/6/e202101277.abstract N2 - Argonaute proteins (AGOs), which play an essential role in cytosolic post-transcriptional gene silencing, have been also reported to function in nuclear processes like transcriptional activation or repression, alternative splicing and, chromatin organization. As most of these studies have been conducted in human cancer cell lines, the relevance of AGOs nuclear functions in the context of mouse early embryonic development remains uninvestigated. Here, we examined a possible role of the AGO1 protein on the distribution of constitutive heterochromatin in mouse embryonic stem cells (mESCs). We observed a specific redistribution of the repressive histone mark H3K9me3 and the heterochromatin protein HP1α, away from pericentromeric regions upon Ago1 depletion. Furthermore, we demonstrated that major satellite transcripts are strongly up-regulated in Ago1_KO mESCs and that their levels are partially restored upon AGO1 rescue. We also observed a similar redistribution of H3K9me3 and HP1α in Drosha_KO mESCs, suggesting a role for microRNAs (miRNAs) in the regulation of heterochromatin distribution in mESCs. Finally, we showed that specific miRNAs with complementarity to major satellites can partially regulate the expression of these transcripts. ER -