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Tunable Transcriptional Interference at the Endogenous Alcohol Dehydrogenase Gene Locus in Drosophila melanogaster
Neighboring sequences of a gene can influence its expression. In the phenomenon known as transcriptional interference, transcription at one region in the genome can repress transcription at a nearby region in cis. Transcriptional interference occurs at a number of eukaryotic loci, including the alco...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Genetics Society of America
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202008/ https://www.ncbi.nlm.nih.gov/pubmed/32213532 http://dx.doi.org/10.1534/g3.119.400937 |
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author | Jorgensen, Victoria Chen, Jingxun Vander Wende, Helen Harris, Devon E. McCarthy, Alicia Breznak, Shane Wong-Deyrup, Siu Wah Chen, Yuzhang Rangan, Prashanth Brar, Gloria Ann Sawyer, Eric M. Chan, Leon Y. Ünal, Elçin |
author_facet | Jorgensen, Victoria Chen, Jingxun Vander Wende, Helen Harris, Devon E. McCarthy, Alicia Breznak, Shane Wong-Deyrup, Siu Wah Chen, Yuzhang Rangan, Prashanth Brar, Gloria Ann Sawyer, Eric M. Chan, Leon Y. Ünal, Elçin |
author_sort | Jorgensen, Victoria |
collection | PubMed |
description | Neighboring sequences of a gene can influence its expression. In the phenomenon known as transcriptional interference, transcription at one region in the genome can repress transcription at a nearby region in cis. Transcriptional interference occurs at a number of eukaryotic loci, including the alcohol dehydrogenase (Adh) gene in Drosophila melanogaster. Adh is regulated by two promoters, which are distinct in their developmental timing of activation. It has been shown using transgene insertion that when the promoter distal from the Adh start codon is deleted, transcription from the proximal promoter becomes de-regulated. As a result, the Adh proximal promoter, which is normally active only during the early larval stages, becomes abnormally activated in adults. Whether this type of regulation occurs in the endogenous Adh context, however, remains unclear. Here, we employed the CRISPR/Cas9 system to edit the endogenous Adh locus and found that removal of the distal promoter also resulted in the untimely expression of the proximal promoter-driven mRNA isoform in adults, albeit at lower levels than previously reported. Importantly, transcription from the distal promoter was sufficient to repress proximal transcription in larvae, and the degree of this repression was dependent on the degree of distal promoter activity. Finally, upregulation of the distal Adh transcript led to the enrichment of histone 3 lysine 36 trimethylation over the Adh proximal promoter. We conclude that the endogenous Adh locus is developmentally regulated by transcriptional interference in a tunable manner. |
format | Online Article Text |
id | pubmed-7202008 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Genetics Society of America |
record_format | MEDLINE/PubMed |
spelling | pubmed-72020082020-05-09 Tunable Transcriptional Interference at the Endogenous Alcohol Dehydrogenase Gene Locus in Drosophila melanogaster Jorgensen, Victoria Chen, Jingxun Vander Wende, Helen Harris, Devon E. McCarthy, Alicia Breznak, Shane Wong-Deyrup, Siu Wah Chen, Yuzhang Rangan, Prashanth Brar, Gloria Ann Sawyer, Eric M. Chan, Leon Y. Ünal, Elçin G3 (Bethesda) Investigations Neighboring sequences of a gene can influence its expression. In the phenomenon known as transcriptional interference, transcription at one region in the genome can repress transcription at a nearby region in cis. Transcriptional interference occurs at a number of eukaryotic loci, including the alcohol dehydrogenase (Adh) gene in Drosophila melanogaster. Adh is regulated by two promoters, which are distinct in their developmental timing of activation. It has been shown using transgene insertion that when the promoter distal from the Adh start codon is deleted, transcription from the proximal promoter becomes de-regulated. As a result, the Adh proximal promoter, which is normally active only during the early larval stages, becomes abnormally activated in adults. Whether this type of regulation occurs in the endogenous Adh context, however, remains unclear. Here, we employed the CRISPR/Cas9 system to edit the endogenous Adh locus and found that removal of the distal promoter also resulted in the untimely expression of the proximal promoter-driven mRNA isoform in adults, albeit at lower levels than previously reported. Importantly, transcription from the distal promoter was sufficient to repress proximal transcription in larvae, and the degree of this repression was dependent on the degree of distal promoter activity. Finally, upregulation of the distal Adh transcript led to the enrichment of histone 3 lysine 36 trimethylation over the Adh proximal promoter. We conclude that the endogenous Adh locus is developmentally regulated by transcriptional interference in a tunable manner. Genetics Society of America 2020-03-25 /pmc/articles/PMC7202008/ /pubmed/32213532 http://dx.doi.org/10.1534/g3.119.400937 Text en Copyright © 2020 Jorgensen et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Investigations Jorgensen, Victoria Chen, Jingxun Vander Wende, Helen Harris, Devon E. McCarthy, Alicia Breznak, Shane Wong-Deyrup, Siu Wah Chen, Yuzhang Rangan, Prashanth Brar, Gloria Ann Sawyer, Eric M. Chan, Leon Y. Ünal, Elçin Tunable Transcriptional Interference at the Endogenous Alcohol Dehydrogenase Gene Locus in Drosophila melanogaster |
title | Tunable Transcriptional Interference at the Endogenous Alcohol Dehydrogenase Gene Locus in Drosophila melanogaster |
title_full | Tunable Transcriptional Interference at the Endogenous Alcohol Dehydrogenase Gene Locus in Drosophila melanogaster |
title_fullStr | Tunable Transcriptional Interference at the Endogenous Alcohol Dehydrogenase Gene Locus in Drosophila melanogaster |
title_full_unstemmed | Tunable Transcriptional Interference at the Endogenous Alcohol Dehydrogenase Gene Locus in Drosophila melanogaster |
title_short | Tunable Transcriptional Interference at the Endogenous Alcohol Dehydrogenase Gene Locus in Drosophila melanogaster |
title_sort | tunable transcriptional interference at the endogenous alcohol dehydrogenase gene locus in drosophila melanogaster |
topic | Investigations |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202008/ https://www.ncbi.nlm.nih.gov/pubmed/32213532 http://dx.doi.org/10.1534/g3.119.400937 |
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