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

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ID: 62472
2019
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Abstract
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.
Reference Key
shuaib2019nuclearcell Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Shuaib, Muhammad;Parsi, Krishna Mohan;Thimma, Manjula;Adroub, Sabir Abdu;Hideya, Kawaji;Seridi, Loqmane;Ghosheh, Yanal;Fort, Alexandre;Fallatah, Bodor;Ravasi, Timothy;Carninci, Piero;Orlando, Valerio;
Journal cell systems
Year 2019
DOI
S2405-4712(19)30313-8
URL
Keywords
non-coding rna gene expression regulation 3d chromatin organization rnai components enhancers nuclear ago1

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