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  Argonaute-1 binds transcriptional enhancers and controls constitutive and alternative splicing in human cells.

Alló, M., Agirre, E., Bessonov, S., Bertucci, P., Acuña, L. G., Buggiano, V., et al. (2014). Argonaute-1 binds transcriptional enhancers and controls constitutive and alternative splicing in human cells. Proceedings of the National Academy of Sciences of the United States of America, 111(44), 15622-15629. doi:10.1073/pnas.1416858111.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0024-42CA-F Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-80EC-F
Genre: Journal Article

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 Creators:
Alló, M., Author
Agirre, E., Author
Bessonov, S.1, Author              
Bertucci, P., Author
Acuña, L. G., Author
Buggiano, V., Author
Bellora, N., Author
Singh, B., Author
Petrilloa, Ezequiel, Author
Blaustein, M., Author
Miñana, B., Author
Dujardin, G., Author
Pozzi, B., Author
Pelisch, F., Author
Bechara, E., Author
Agafonov, D. E.1, Author              
Srebrow, A., Author
Lührmann, R.1, Author              
Valcárcel, J., Author
Eyras, E., Author
Kornblihtt, A. R., Author more..
Affiliations:
1Department of Cellular Biochemistry, MPI for biophysical chemistry, Max Planck Society, ou_578576              

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Free keywords: Argonaute proteins; transcriptional enhancers; alternative splicing
 Abstract: The roles of Argonaute proteins in cytoplasmic microRNA and RNAi pathways are well established. However, their implication in small RNA-mediated transcriptional gene silencing in the mammalian cell nucleus is less understood. We have recently shown that intronic siRNAs cause chromatin modifications that inhibit RNA polymerase II elongation and modulate alternative splicing in an Argonaute-1 (AGO1)-dependent manner. Here we used chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) to investigate the genome-wide distribution of AGO1 nuclear targets. Unexpectedly, we found that about 80% of AGO1 clusters are associated with cell-type-specific transcriptional enhancers, most of them (73%) overlapping active enhancers. This association seems to be mediated by long, rather than short, enhancer RNAs and to be more prominent in intragenic, rather than intergenic, enhancers. Paradoxically, crossing ChIP-seq with RNA-seq data upon AGO1 depletion revealed that enhancer-bound AGO1 is not linked to the global regulation of gene transcription but to the control of constitutive and alternative splicing, which was confirmed by an individual gene analysis explaining how AGO1 controls inclusion levels of the cassette exon 107 in the SYNE2 gene.

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Language(s): eng - English
 Dates: 2014-10-132014-11-04
 Publication Status: Published in print
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 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1073/pnas.1416858111
 Degree: -

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Title: Proceedings of the National Academy of Sciences of the United States of America
Source Genre: Journal
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Pages: - Volume / Issue: 111 (44) Sequence Number: - Start / End Page: 15622 - 15629 Identifier: -