Regulating retrotransposon activity through the use of alternative transcription start sites

Jenna Persson; Babett Steglich; Agata Smialowska; Mette Boyd; Jette Bornholdt Lange; Robin Andersson; Catherine Schurra; Benoit Arcangioli; Albin Gustav Sandelin; Olaf Nielsen; Karl Ekwall

doi:10.15252/embr.201541866

Regulating retrotransposon activity through the use of alternative transcription start sites

Jenna Persson, Babett Steglich, Agata Smialowska, Mette Boyd, Jette Bornholdt Lange, Robin Andersson, Catherine Schurra, Benoit Arcangioli, Albin Gustav Sandelin, Olaf Nielsen, Karl Ekwall

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Abstract

Retrotransposons, the ancestors of retroviruses, have the potential for gene disruption and genomic takeover if not kept in check. Paradoxically, although host cells repress these elements by multiple mechanisms, they are transcribed and are even activated under stress conditions. Here, we describe a new mechanism of retrotransposon regulation through transcription start site (TSS) selection by altered nucleosome occupancy. We show that Fun30 chromatin remodelers cooperate to maintain a high level of nucleosome occupancy at retrotransposon-flanking long terminal repeat (LTR) elements. This enforces the use of a downstream TSS and the production of a truncated RNA incapable of reverse transcription and retrotransposition. However, in stressed cells, nucleosome occupancy at LTR elements is reduced, and the TSS shifts to allow for productive transcription. We propose that controlled retrotransposon transcription from a nonproductive TSS allows for rapid stress-induced activation, while preventing uncontrolled transposon activity in the genome. Synopsis Retrotransposons can be activated under cellular stress conditions or at specific developmental stages. This study reveals a new mechanism of dynamic retrotransposon regulation by alternative transcription start site (TSS) selection. Fun30 chromatin remodelers maintain a critical nucleosome in LTR elements leading to the usage of a downstream TSS and the production of RNA incapable of reverse transcription and retrotransposition. In stressed cells, or in Fun30 mutants, the LTR nucleosome occupancy is reduced and the TSS shifts to allow for productive transcription and retrotransposition. Retrotransposons can be activated under cellular stress conditions or at specific developmental stages. This study reveals a new mechanism of dynamic retrotransposon regulation by alternative transcription start site (TSS) selection.

Original language	English
Journal	E M B O Reports
Volume	17
Issue number	5
Pages (from-to)	753-768
Number of pages	16
ISSN	1469-221X
DOIs	https://doi.org/10.15252/embr.201541866
Publication status	Published - 1 May 2016

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@article{cb5f64f8f1ce439dbf124e1072bd78f2,

title = "Regulating retrotransposon activity through the use of alternative transcription start sites",

abstract = "Retrotransposons, the ancestors of retroviruses, have the potential for gene disruption and genomic takeover if not kept in check. Paradoxically, although host cells repress these elements by multiple mechanisms, they are transcribed and are even activated under stress conditions. Here, we describe a new mechanism of retrotransposon regulation through transcription start site (TSS) selection by altered nucleosome occupancy. We show that Fun30 chromatin remodelers cooperate to maintain a high level of nucleosome occupancy at retrotransposon-flanking long terminal repeat (LTR) elements. This enforces the use of a downstream TSS and the production of a truncated RNA incapable of reverse transcription and retrotransposition. However, in stressed cells, nucleosome occupancy at LTR elements is reduced, and the TSS shifts to allow for productive transcription. We propose that controlled retrotransposon transcription from a nonproductive TSS allows for rapid stress-induced activation, while preventing uncontrolled transposon activity in the genome. Synopsis Retrotransposons can be activated under cellular stress conditions or at specific developmental stages. This study reveals a new mechanism of dynamic retrotransposon regulation by alternative transcription start site (TSS) selection. Fun30 chromatin remodelers maintain a critical nucleosome in LTR elements leading to the usage of a downstream TSS and the production of RNA incapable of reverse transcription and retrotransposition. In stressed cells, or in Fun30 mutants, the LTR nucleosome occupancy is reduced and the TSS shifts to allow for productive transcription and retrotransposition. Retrotransposons can be activated under cellular stress conditions or at specific developmental stages. This study reveals a new mechanism of dynamic retrotransposon regulation by alternative transcription start site (TSS) selection.",

author = "Jenna Persson and Babett Steglich and Agata Smialowska and Mette Boyd and Lange, {Jette Bornholdt} and Robin Andersson and Catherine Schurra and Benoit Arcangioli and Sandelin, {Albin Gustav} and Olaf Nielsen and Karl Ekwall",

note = "{\textcopyright} 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license.",

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doi = "10.15252/embr.201541866",

language = "English",

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T1 - Regulating retrotransposon activity through the use of alternative transcription start sites

AU - Persson, Jenna

AU - Steglich, Babett

AU - Smialowska, Agata

AU - Boyd, Mette

AU - Lange, Jette Bornholdt

AU - Andersson, Robin

AU - Schurra, Catherine

AU - Arcangioli, Benoit

AU - Sandelin, Albin Gustav

AU - Nielsen, Olaf

AU - Ekwall, Karl

PY - 2016/5/1

Y1 - 2016/5/1

N2 - Retrotransposons, the ancestors of retroviruses, have the potential for gene disruption and genomic takeover if not kept in check. Paradoxically, although host cells repress these elements by multiple mechanisms, they are transcribed and are even activated under stress conditions. Here, we describe a new mechanism of retrotransposon regulation through transcription start site (TSS) selection by altered nucleosome occupancy. We show that Fun30 chromatin remodelers cooperate to maintain a high level of nucleosome occupancy at retrotransposon-flanking long terminal repeat (LTR) elements. This enforces the use of a downstream TSS and the production of a truncated RNA incapable of reverse transcription and retrotransposition. However, in stressed cells, nucleosome occupancy at LTR elements is reduced, and the TSS shifts to allow for productive transcription. We propose that controlled retrotransposon transcription from a nonproductive TSS allows for rapid stress-induced activation, while preventing uncontrolled transposon activity in the genome. Synopsis Retrotransposons can be activated under cellular stress conditions or at specific developmental stages. This study reveals a new mechanism of dynamic retrotransposon regulation by alternative transcription start site (TSS) selection. Fun30 chromatin remodelers maintain a critical nucleosome in LTR elements leading to the usage of a downstream TSS and the production of RNA incapable of reverse transcription and retrotransposition. In stressed cells, or in Fun30 mutants, the LTR nucleosome occupancy is reduced and the TSS shifts to allow for productive transcription and retrotransposition. Retrotransposons can be activated under cellular stress conditions or at specific developmental stages. This study reveals a new mechanism of dynamic retrotransposon regulation by alternative transcription start site (TSS) selection.

AB - Retrotransposons, the ancestors of retroviruses, have the potential for gene disruption and genomic takeover if not kept in check. Paradoxically, although host cells repress these elements by multiple mechanisms, they are transcribed and are even activated under stress conditions. Here, we describe a new mechanism of retrotransposon regulation through transcription start site (TSS) selection by altered nucleosome occupancy. We show that Fun30 chromatin remodelers cooperate to maintain a high level of nucleosome occupancy at retrotransposon-flanking long terminal repeat (LTR) elements. This enforces the use of a downstream TSS and the production of a truncated RNA incapable of reverse transcription and retrotransposition. However, in stressed cells, nucleosome occupancy at LTR elements is reduced, and the TSS shifts to allow for productive transcription. We propose that controlled retrotransposon transcription from a nonproductive TSS allows for rapid stress-induced activation, while preventing uncontrolled transposon activity in the genome. Synopsis Retrotransposons can be activated under cellular stress conditions or at specific developmental stages. This study reveals a new mechanism of dynamic retrotransposon regulation by alternative transcription start site (TSS) selection. Fun30 chromatin remodelers maintain a critical nucleosome in LTR elements leading to the usage of a downstream TSS and the production of RNA incapable of reverse transcription and retrotransposition. In stressed cells, or in Fun30 mutants, the LTR nucleosome occupancy is reduced and the TSS shifts to allow for productive transcription and retrotransposition. Retrotransposons can be activated under cellular stress conditions or at specific developmental stages. This study reveals a new mechanism of dynamic retrotransposon regulation by alternative transcription start site (TSS) selection.

U2 - 10.15252/embr.201541866

DO - 10.15252/embr.201541866

M3 - Journal article

C2 - 26902262

SN - 1469-221X

VL - 17

SP - 753

EP - 768

JO - E M B O Reports

JF - E M B O Reports

IS - 5

ER -

Regulating retrotransposon activity through the use of alternative transcription start sites

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