Authors: Muhammad Shuaib, Krishna Mohan Parsi, Hideya Kawaji, Manjula Thimma, Sabir Abdu Adroub, Alexandre Fort, Yanal Ghosheh, Tomohiro Yamazaki, Taro Mannen, Loqmane Seridi, Bodor Fallatah, Waad Albawardi, Timothy Ravasi, Piero Carninci, Tetsuro Hirose, Valerio Orlando

Institutions: 

  • King Abdullah University of Science and Technology (KAUST), BESE Division, KAUST Environmental Epigenetics Program, Thuwal, 23955-6900, Saudi Arabia
  • IRCSS Fondazione Santa Lucia, Epigenetics and Genome Reprogramming, Rome, Italy.
  • RIKEN Center for Life Science Technologies, Division of Genomic Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
  • Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan

Publication: Cell Systems

Date: January 2019

Full paper: https://doi.org/10.1016/j.cels.2019.09.005

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.