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

Muhammad Shuaib, Krishna Mohan Parsi, Manjula Thimma, Sabir Adroub, Hideya Kawaji, Loqmane Seridi, Yanal Ghosheh, Alexandre Fort, Bodor Fallatah, Timothy Ravasi, Piero Carninci, Valerio Orlando

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6 Scopus citations

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.
Original languageEnglish (US)
Pages (from-to)446-458.e6
Number of pages457999555
JournalCell systems
Volume9
Issue number5
DOIs
StatePublished - Oct 21 2019

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  • Homo sapiens Transcriptome or Gene expression

    Shuaib, M. (Creator), Parsi, K. M. (Creator), Thimma, M. (Creator), Adroub, S. (Creator), Kawaji, H. (Creator), Seridi, L. (Creator), Ghosheh, Y. (Creator), Fort, A. (Creator), Fallatah, B. (Creator), Ravasi, T. (Creator), Carninci, P. (Creator), Orlando, V. (Creator), Parsi, K. M. (Creator), Adroub, S. (Creator), Kawaji, H. (Creator), Fort, A. (Creator), Ravasi, T. (Creator) & Carninci, P. (Creator), NCBI, May 20 2019

    Dataset

  • Studying the role of nuclear AGO1 in Chromatin Organisation

    Shuaib, M. (Creator), Parsi, K. M. (Creator), Thimma, M. (Creator), Adroub, S. (Creator), Kawaji, H. (Creator), Seridi, L. (Creator), Ghosheh, Y. (Creator), Fort, A. (Creator), Fallatah, B. (Creator), Ravasi, T. (Creator), Carninci, P. (Creator), Orlando, V. (Creator), Parsi, K. M. (Creator), Kawaji, H. (Creator), Fort, A. (Creator), Ravasi, T. (Creator) & Carninci, P. (Creator), NCBI, Aug 17 2017

    Dataset

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