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bioRxiv · 10.1101/455733

TFIIIC dynamically binds Alu elements to control gene expression through chromatin looping

Ferrari, R.·Llobet Cucalon, L. I.·Di Vona, C.·Vidal, E.·Lioutas, A.·Le Dilly, F.·Oliete, J. Q.·Dieci, G.·Teichmann, M.·de la Luna, S.·Beato, M.
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Abstract

Folding of the mammalian genome is governed by architectural proteins, such as CTCF. TFIIIC, a RNA polymerase III transcription factor, has been identified as an insulator but its role in genome topology is totally unknown. Here, we show that TFIIIC establishes long-range genomic interactions that affect gene expression. Upon serum starvation (SS), TFIIIC occupancy increases at Alu elements (AEs) near promoters of cell cycle-related genes. Bound AEs become H3K18 hyper-acetylated and fold to contact distal pre-loaded CTCF sites near other cell cycle genes. The promoters of these genes also become hyper-acetylated ensuring their basal transcription during SS and their increased expression during serum re-exposure. Ablation of TFIIIC or deletion of the TFIIIC-bound AE that loops to the G2/M cycling F (CCNF) locus affects its expression and nuclear positioning. These results illustrate a novel function of human TFIIIC in changing 3D genome topology through the epigenetic state of AEs.\n\nHighlightsO_LISerum starvation enhances TFIIIC binding to Alu Elements (AEs) near cell cycle genes\nC_LIO_LIBinding of TFIIIC increases H3K18 acetylation over the bound AE\nC_LIO_LITFIIIC-mediated looping to distal genes favors their reactivation upon serum addition\nC_LIO_LILong-range TFIIIC interactions tune cell cycle genes expression through nuclear repositioning\nC_LI\n\nGraphical abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=64 SRC=\"FIGDIR/small/455733_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (22K):\norg.highwire.dtl.DTLVardef@917ee4org.highwire.dtl.DTLVardef@21d0fborg.highwire.dtl.DTLVardef@1f1a17org.highwire.dtl.DTLVardef@1e9df24_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Ferrari, R., Llobet Cucalon, L. I., Di Vona, C., Vidal, E., Lioutas, A., Le Dilly, F., Oliete, J. Q., Dieci, G., Teichmann, M., de la Luna, S., Beato, M.. 2018-10-29. TFIIIC dynamically binds Alu elements to control gene expression through chromatin looping. https://doi.org/10.1101/455733

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