INVESTIGADORES
BELLORA nicolas
artículos
Título:
Argonaute-1 binds transcriptional enhancers and controls constitutive and alternative splicing in human cells
Autor/es:
ALLÓ, M; AGIRRE, E; BESSONOV, S; BERTUCCI, P; ACUÑA, L. G.; BUGGIANO, V.; BELLORA, N.; VALCÁRCEL, J.; EYRAS, E. ; KORNBLIHTT, A. R.
Revista:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Editorial:
NATL ACAD SCIENCES
Referencias:
Lugar: Washington DC, USA; Año: 2014
ISSN:
0027-8424
Resumen:
The roles of Argonaute proteins in cytoplasmic microRNA and RNAipathways are well established. However, their implication in smallRNA-mediated transcriptional gene silencing in the mammalian cellnucleus is less understood. We have recently shown that intronicsiRNAs cause chromatin modifications that inhibit RNA polymeraseII elongation and modulate alternative splicing in an Argonaute-1(AGO1)-dependent manner. Here we used chromatin immunoprecipitationfollowed by deep sequencing (ChIP-seq) to investigate thegenome-wide distribution of AGO1 nuclear targets. Unexpectedly,we found that about 80% of AGO1 clusters are associated withcell-type-specific transcriptional enhancers, most of them (73%)overlapping active enhancers. This association seems to be mediatedby long, rather than short, enhancer RNAs and to be moreprominent in intragenic, rather than intergenic, enhancers. Paradoxically,crossing ChIP-seq with RNA-seq data upon AGO1 depletionrevealed that enhancer-bound AGO1 is not linked to theglobal regulation of gene transcription but to the control of constitutiveand alternative splicing, which was confirmed by an individualgene analysis explaining how AGO1 controls inclusionlevels of the cassette exon 107 in the SYNE2 gene.