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

doi:10.1016/j.cels.2019.09.005

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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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 language	English (US)
Pages (from-to)	446-458.e6
Number of pages	457999555
Journal	Cell systems
Volume	9
Issue number	5
DOIs	https://doi.org/10.1016/j.cels.2019.09.005
State	Published - Oct 21 2019

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: M.S. conceived this study, designed and performed experiments, analyzedthe data, and wrote the manuscript with input from all the authors. K.M.P.conceived this study, designed, performed experiments, and analyzed thedata. S.A.A. with M.S. performed Hi-C experiments. M.T. and H.K. performedcomputational analyses of CAGE-seq and ChIP-seq data. L.S. and T.R. per-formed computational analyses of ChIP-seq and CAGE-seq data integration.Y.G. performed computational analyses of RIP-seq and ChIP-seq integration.A.F. contributed in RIP-seq experiments. B.F. helped in western blotting. P.C.and H.K. produced and analyzed the CAGE-seq experiment. V.O. conceivedthis study, designed experiments, and wrote the manuscript.

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10.1016/j.cels.2019.09.005

https://repository.kaust.edu.sa/bitstream/10754/659968/1/1-s2.0-S2405471219303138-main.pdf

Cite this

@article{cc0e16f84d49446789053159056e1d83,

title = "Nuclear AGO1 Regulates Gene Expression by Affecting Chromatin Architecture in Human Cells.",

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.",

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

note = "KAUST Repository Item: Exported on 2020-10-01 Acknowledgements: M.S. conceived this study, designed and performed experiments, analyzedthe data, and wrote the manuscript with input from all the authors. K.M.P.conceived this study, designed, performed experiments, and analyzed thedata. S.A.A. with M.S. performed Hi-C experiments. M.T. and H.K. performedcomputational analyses of CAGE-seq and ChIP-seq data. L.S. and T.R. per-formed computational analyses of ChIP-seq and CAGE-seq data integration.Y.G. performed computational analyses of RIP-seq and ChIP-seq integration.A.F. contributed in RIP-seq experiments. B.F. helped in western blotting. P.C.and H.K. produced and analyzed the CAGE-seq experiment. V.O. conceivedthis study, designed experiments, and wrote the manuscript.",

year = "2019",

month = oct,

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doi = "10.1016/j.cels.2019.09.005",

language = "English (US)",

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T1 - Nuclear AGO1 Regulates Gene Expression by Affecting Chromatin Architecture in Human Cells.

AU - Shuaib, Muhammad

AU - Parsi, Krishna Mohan

AU - Thimma, Manjula

AU - Adroub, Sabir

AU - Kawaji, Hideya

AU - Seridi, Loqmane

AU - Ghosheh, Yanal

AU - Fort, Alexandre

AU - Fallatah, Bodor

AU - Ravasi, Timothy

AU - Carninci, Piero

AU - Orlando, Valerio

N1 - KAUST Repository Item: Exported on 2020-10-01 Acknowledgements: M.S. conceived this study, designed and performed experiments, analyzedthe data, and wrote the manuscript with input from all the authors. K.M.P.conceived this study, designed, performed experiments, and analyzed thedata. S.A.A. with M.S. performed Hi-C experiments. M.T. and H.K. performedcomputational analyses of CAGE-seq and ChIP-seq data. L.S. and T.R. per-formed computational analyses of ChIP-seq and CAGE-seq data integration.Y.G. performed computational analyses of RIP-seq and ChIP-seq integration.A.F. contributed in RIP-seq experiments. B.F. helped in western blotting. P.C.and H.K. produced and analyzed the CAGE-seq experiment. V.O. conceivedthis study, designed experiments, and wrote the manuscript.

PY - 2019/10/21

Y1 - 2019/10/21

N2 - 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.

AB - 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.

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U2 - 10.1016/j.cels.2019.09.005

DO - 10.1016/j.cels.2019.09.005

M3 - Article

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SN - 2405-4712

VL - 9

SP - 446-458.e6

JO - Cell systems

JF - Cell systems

IS - 5

ER -

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

Abstract

Bibliographical note

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Homo sapiens Transcriptome or Gene expression

Studying the role of nuclear AGO1 in Chromatin Organisation

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

Abstract

Bibliographical note

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Homo sapiens Transcriptome or Gene expression

Studying the role of nuclear AGO1 in Chromatin Organisation

Cite this