title: ARGONAUTE2 cooperates with SWI/SNF complex to determine nucleosome occupancy at human Transcription Start Sites.
abstract: Argonaute (AGO) proteins have a well-established role in post-transcriptional regulation of gene expression as key component of the RNA silencing pathways. Recent evidence involves AGO proteins in mammalian nuclear processes such as transcription and splicing, though the mechanistic aspects of AGO nuclear functions remain largely elusive. Here, by SILAC-based interaction proteomics, we identify the chromatin-remodelling complex SWI/SNF as a novel AGO2 interactor in human cells. Moreover, we show that nuclear AGO2 is loaded with a novel class of Dicer-dependent short RNAs (sRNAs), that we called swiRNAs, which map nearby the Transcription Start Sites (TSSs) bound by SWI/SNF. The knock-down of AGO2 decreases nucleosome occupancy at the first nucleosome located downstream of TSSs in a swiRNA-dependent manner. Our findings indicate that in human cells AGO2 binds SWI/SNF and a novel class of sRNAs to establish nucleosome occupancy on target TSSs.
authors.affiliation: Dipartimento di Biotecnologie Cellulari ed Ematologia, 'Sapienza' Università di Roma, Rome 00161, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Carissimi
authors.affiliation: Dipartimento di Biotecnologie Cellulari ed Ematologia, 'Sapienza' Università di Roma, Rome 00161, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Laudadio
authors.affiliation: Dipartimento di Biotecnologie Cellulari ed Ematologia, 'Sapienza' Università di Roma, Rome 00161, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Cipolletta
authors.affiliation: Dipartimento di Biotecnologie Cellulari ed Ematologia, 'Sapienza' Università di Roma, Rome 00161, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Gioiosa
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology (IEO), Milan 20139, Italy.
authors.forename: Marija
authors.initials: M
authors.lastname: Mihailovich
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology (IEO), Milan 20139, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bonaldi
authors.affiliation: Dipartimento di Biotecnologie Cellulari ed Ematologia, 'Sapienza' Università di Roma, Rome 00161, Italy giuseppe.macino@uniroma1.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Macino
authors.affiliation: Dipartimento di Biotecnologie Cellulari ed Ematologia, 'Sapienza' Università di Roma, Rome 00161, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Fulci
mesh_terms: D060565:Argonaute Proteins / Q000378:metabolism*; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D002853:Chromatography, Liquid; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D009707:Nucleosomes / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D053719:Tandem Mass Spectrometry; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: C466422:AGO2 protein, human; D060565:Argonaute Proteins; D004268:DNA-Binding Proteins; D009707:Nucleosomes; D034741:RNA, Small Interfering; C499336:SMARCA1 protein, human; D014157:Transcription Factors