TFIIIC Binding to Alu Elements Controls Gene Expression via Chromatin Looping and Histone Acetylation.

Molecular cell 2020 Feb 06

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How repetitive elements, epigenetic modifications, and architectural proteins interact ensuring proper genome expression remains poorly understood. Here, we report regulatory mechanisms unveiling a central role of Alu elements (AEs) and RNA polymerase III transcription factor C (TFIIIC) in structurally and functionally modulating the genome via chromatin looping and histone acetylation. Upon serum deprivation, a subset of AEs pre-marked by the activity-dependent neuroprotector homeobox Protein (ADNP) and located near cell-cycle genes recruits TFIIIC, which alters their chromatin accessibility by direct acetylation of histone H3 lysine-18 (H3K18). This facilitates the contacts of AEs with distant CTCF sites near promoter of other cell-cycle genes, which also become hyperacetylated at H3K18. These changes ensure basal transcription of cell-cycle genes and are critical for their re-activation upon serum re-exposure. Our study reveals how direct manipulation of the epigenetic state of AEs by a general transcription factor regulates 3D genome folding and expression. Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Roberto Ferrari, Lara Isabel de Llobet Cucalon, Chiara Di Vona, François Le Dilly, Enrique Vidal, Antonios Lioutas, Javier Quilez Oliete, Laura Jochem, Erin Cutts, Giorgio Dieci, Alessandro Vannini, Martin Teichmann, Susana de la Luna, Miguel Beato. TFIIIC Binding to Alu Elements Controls Gene Expression via Chromatin Looping and Histone Acetylation. Molecular cell. 2020 Feb 06;77(3):475-487.e11