UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Co-option of endogenous retroviruses through genetic escape from TRIM28 repression

Enriquez-Gasca, Rocio; Gould, Poppy A; Tunbak, Hale; Conde, Lucia; Herrero, Javier; Chittka, Alexandra; Beck, Christine R; ... Rowe, Helen M; + view all (2023) Co-option of endogenous retroviruses through genetic escape from TRIM28 repression. Cell Reports , 42 (6) , Article 112625. 10.1016/j.celrep.2023.112625. Green open access

[thumbnail of PIIS2211124723006368.pdf]
Preview
Text
PIIS2211124723006368.pdf - Published Version

Download (4MB) | Preview

Abstract

Endogenous retroviruses (ERVs) have rewired host gene networks. To explore the origins of co-option, we employed an active murine ERV, IAPEz, and an embryonic stem cell (ESC) to neural progenitor cell (NPC) differentiation model. Transcriptional silencing via TRIM28 maps to a 190 bp sequence encoding the intracisternal A-type particle (IAP) signal peptide, which confers retrotransposition activity. A subset of "escapee" IAPs (∼15%) exhibits significant genetic divergence from this sequence. Canonical repressed IAPs succumb to a previously undocumented demarcation by H3K9me3 and H3K27me3 in NPCs. Escapee IAPs, in contrast, evade repression in both cell types, resulting in their transcriptional derepression, particularly in NPCs. We validate the enhancer function of a 47 bp sequence within the U3 region of the long terminal repeat (LTR) and show that escapee IAPs convey an activating effect on nearby neural genes. In sum, co-opted ERVs stem from genetic escapees that have lost vital sequences required for both TRIM28 restriction and autonomous retrotransposition.

Type: Article
Title: Co-option of endogenous retroviruses through genetic escape from TRIM28 repression
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2023.112625
Publisher version: https://doi.org/10.1016/j.celrep.2023.112625
Language: English
Additional information: © 2023 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: CP: Developmental biology, CP: Stem cell research, ERVs, IAPs, KRAB-zinc finger proteins, TRIM28, cancer, co-option, endogenous retroviruses, enhancers, epigenetic silencing, exaptation, intracisternal A-type particles, retrotransposition, retrotransposon
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: https://discovery.ucl.ac.uk/id/eprint/10171995
Downloads since deposit
14Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item