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Nup98-dependent transcriptional memory is established independently of transcription

Cellular ability to mount an enhanced transcriptional response upon repeated exposure to external cues is termed transcriptional memory, which can be maintained epigenetically through cell divisions and can depend on a nuclear pore component Nup98. The majority of mechanistic knowledge on transcript...

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Autores principales: Pascual-Garcia, Pau, Little, Shawn C, Capelson, Maya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8923668/
https://www.ncbi.nlm.nih.gov/pubmed/35289742
http://dx.doi.org/10.7554/eLife.63404
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author Pascual-Garcia, Pau
Little, Shawn C
Capelson, Maya
author_facet Pascual-Garcia, Pau
Little, Shawn C
Capelson, Maya
author_sort Pascual-Garcia, Pau
collection PubMed
description Cellular ability to mount an enhanced transcriptional response upon repeated exposure to external cues is termed transcriptional memory, which can be maintained epigenetically through cell divisions and can depend on a nuclear pore component Nup98. The majority of mechanistic knowledge on transcriptional memory has been derived from bulk molecular assays. To gain additional perspective on the mechanism and contribution of Nup98 to memory, we used single-molecule RNA FISH (smFISH) to examine the dynamics of transcription in Drosophila cells upon repeated exposure to the steroid hormone ecdysone. We combined smFISH with mathematical modeling and found that upon hormone exposure, cells rapidly activate a low-level transcriptional response, but simultaneously begin a slow transition into a specialized memory state characterized by a high rate of expression. Strikingly, our modeling predicted that this transition between non-memory and memory states is independent of the transcription stemming from initial activation. We confirmed this prediction experimentally by showing that inhibiting transcription during initial ecdysone exposure did not interfere with memory establishment. Together, our findings reveal that Nup98’s role in transcriptional memory is to stabilize the forward rate of conversion from low to high expressing state, and that induced genes engage in two separate behaviors – transcription itself and the establishment of epigenetically propagated transcriptional memory.
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spelling pubmed-89236682022-03-16 Nup98-dependent transcriptional memory is established independently of transcription Pascual-Garcia, Pau Little, Shawn C Capelson, Maya eLife Chromosomes and Gene Expression Cellular ability to mount an enhanced transcriptional response upon repeated exposure to external cues is termed transcriptional memory, which can be maintained epigenetically through cell divisions and can depend on a nuclear pore component Nup98. The majority of mechanistic knowledge on transcriptional memory has been derived from bulk molecular assays. To gain additional perspective on the mechanism and contribution of Nup98 to memory, we used single-molecule RNA FISH (smFISH) to examine the dynamics of transcription in Drosophila cells upon repeated exposure to the steroid hormone ecdysone. We combined smFISH with mathematical modeling and found that upon hormone exposure, cells rapidly activate a low-level transcriptional response, but simultaneously begin a slow transition into a specialized memory state characterized by a high rate of expression. Strikingly, our modeling predicted that this transition between non-memory and memory states is independent of the transcription stemming from initial activation. We confirmed this prediction experimentally by showing that inhibiting transcription during initial ecdysone exposure did not interfere with memory establishment. Together, our findings reveal that Nup98’s role in transcriptional memory is to stabilize the forward rate of conversion from low to high expressing state, and that induced genes engage in two separate behaviors – transcription itself and the establishment of epigenetically propagated transcriptional memory. eLife Sciences Publications, Ltd 2022-03-15 /pmc/articles/PMC8923668/ /pubmed/35289742 http://dx.doi.org/10.7554/eLife.63404 Text en © 2022, Pascual-Garcia et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Chromosomes and Gene Expression
Pascual-Garcia, Pau
Little, Shawn C
Capelson, Maya
Nup98-dependent transcriptional memory is established independently of transcription
title Nup98-dependent transcriptional memory is established independently of transcription
title_full Nup98-dependent transcriptional memory is established independently of transcription
title_fullStr Nup98-dependent transcriptional memory is established independently of transcription
title_full_unstemmed Nup98-dependent transcriptional memory is established independently of transcription
title_short Nup98-dependent transcriptional memory is established independently of transcription
title_sort nup98-dependent transcriptional memory is established independently of transcription
topic Chromosomes and Gene Expression
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8923668/
https://www.ncbi.nlm.nih.gov/pubmed/35289742
http://dx.doi.org/10.7554/eLife.63404
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