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Mol Cell. 2019 Nov 20. pii: S1097-2765(19)30798-1. doi: 10.1016/j.molcel.2019.10.020. [Epub ahead of print]

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

Author information

1
Center for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Dr. Aiguader 88, Barcelona 08003, Spain. Electronic address: roberto.ferrari@crg.eu.
2
Center for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Dr. Aiguader 88, Barcelona 08003, Spain.
3
Center for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Dr. Aiguader 88, Barcelona 08003, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain.
4
The Institute of Cancer Research (ICR), London, UK.
5
Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy.
6
The Institute of Cancer Research (ICR), London, UK; Human Technopole. Via Cristina Belgioioso, 171, 20157 Milano MI, Italy.
7
Université de Bordeaux, INSERM U1212 CNRS UMR 5320 146, Bordeaux, France.
8
Center for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Dr. Aiguader 88, Barcelona 08003, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain; ICREA, Pg. Lluis Companys 23, Barcelona 08010, Spain.
9
Center for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Dr. Aiguader 88, Barcelona 08003, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain. Electronic address: miguel.beato@crg.eu.

Abstract

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.

KEYWORDS:

3D genome structure; ADPN; Alu elements; CTCF; H3K18ac; Pol II; TFIIIC; breast cancer; cell cycle; serum starvation

PMID:
31759822
DOI:
10.1016/j.molcel.2019.10.020
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