CANTARELLA, Simona; VEZZOLI, Marco; CARNEVALI, Davide; MORSELLI, Marco; ZEMKE, Nathan R; MONTANINI, Barbara; DAUSSY, Coralie F; WODRICH, Harald; TEICHMANN, Martin; PELLEGRINI, Matteo; BERK, Arnold J; DIECI, Giorgio; FERRARI, Roberto

doi:10.1093/nar/gkae615

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Article de revue

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Nucleic Acids Research. 2024-09-09, vol. 52, n° 16, p. 9481-9500

Résumé en anglais

Alu retrotransposons, which form the largest family of mobile DNA elements in the human genome, have recently come to attention as a potential source of regulatory novelties, most notably by participating in enhancer function. Even though Alu transcription by RNA polymerase III is subjected to tight epigenetic silencing, their expression has long been known to increase in response to various types of stress, including viral infection. Here we show that, in primary human fibroblasts, adenovirus small e1a triggered derepression of hundreds of individual Alus by promoting TFIIIB recruitment by Alu-bound TFIIIC. Epigenome profiling revealed an e1a-induced decrease of H3K27 acetylation and increase of H3K4 monomethylation at derepressed Alus, making them resemble poised enhancers. The enhancer nature of e1a-targeted Alus was confirmed by the enrichment, in their upstream regions, of the EP300/CBP acetyltransferase, EP400 chromatin remodeler and YAP1 and FOS transcription factors. The physical interaction of e1a with EP400 was critical for Alu derepression, which was abrogated upon EP400 ablation. Our data suggest that e1a targets a subset of enhancer Alus whose transcriptional activation, which requires EP400 and is mediated by the e1a-EP400 interaction, may participate in the manipulation of enhancer activity by adenoviruses.< Réduire

Mots clés en anglais

Humans

Enhancer Elements

Genetic

Alu Elements

Transcription Factors

Adenovirus E1A Proteins

DNA-Binding Proteins

DNA Helicases

Transcription Factor AP-1

Chromatin Assembly and Disassembly

YAP-Signaling Proteins

Adaptor Proteins

Signal Transducing

Cell Cycle Proteins

Transcriptional Activation

Phosphoproteins

Cells

Cultured

Fibroblasts

Histones

Nuclear Proteins

Transcription Factors

TFIII

URI

https://oskar-bordeaux.fr/handle/20.500.12278/202012

DOI

http://dx.doi.org/10.1093/nar/gkae615

Unités de recherche

MFP (Laboratoire Microbiologie Fondamentale et Pathogénicité) - UMR 5234

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Adenovirus small E1A directs activation of Alu transcription at YAP/TEAD- and AP-1-bound enhancers through interactions with the EP400 chromatin remodeler.

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Mots clés en anglais

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