Nuclear AGO1 Regulates Gene Expression by Affecting Chromatin Architecture in Human Cells

by Muhammad Shuaib, Krishna MohanParsi, Manjula Thimma, Sabir Abdu Adroub, Hideya Kawaji, Loqmane Seridi, Yanal Ghosheh, Alexandre Fort, Bodor Fallatah, Piero Carninci, Valerio Orlando
Year: 2019 DOI:

Extra Information

Cell Syst. 2019 Nov 27;9(5):446-458.e6. doi: 10.1016/j.cels.2019.09.005. Epub 2019 Oct 16.PMID: 31629687


The impact of mammalian RNA interference components, particularly, Argonaute proteins, on chromatin organization is unexplored. Recent reports indicate that AGO1 association with chromatin appears to influence gene expression. To uncover the role of AGO1 in the nucleus, we used a combination of genome-wide approaches in control and AGO1-depleted HepG2 cells. We found that AGO1 strongly associates with active enhancers and RNA being produced at those sites. Hi-C analysis revealed AGO1 enrichment at the boundaries of topologically associated domains (TADs). By Hi-C in AGO1 knockdown cells, we observed changes in chromatin organization, including TADs and A/B compartment mixing, specifically in AGO1-bound regions. Distinct groups of genes and especially eRNA transcripts located within differentially interacting loci showed altered expression upon AGO1 depletion. Moreover, AGO1 association with enhancers is dependent on eRNA transcription. Collectively, our data suggest that enhancer-associated AGO1 contributes to the fine-tuning of chromatin architecture and gene expression in human cells.


RNAi components nuclear AGO1 non-coding RNA enhancers 3D chromatin organization gene expression regulation