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Expression in Aneuploid Drosophila S2 Cells
Extensive departures from balanced gene dose in aneuploids are highly deleterious. However, we know very little about the relationship between gene copy number and expression in aneuploid cells. We determined copy number and transcript abundance (expression) genome-wide in Drosophila S2 cells by DNA...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2826376/ https://www.ncbi.nlm.nih.gov/pubmed/20186269 http://dx.doi.org/10.1371/journal.pbio.1000320 |
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author | Zhang, Yu Malone, John H. Powell, Sara K. Periwal, Vipul Spana, Eric MacAlpine, David M. Oliver, Brian |
author_facet | Zhang, Yu Malone, John H. Powell, Sara K. Periwal, Vipul Spana, Eric MacAlpine, David M. Oliver, Brian |
author_sort | Zhang, Yu |
collection | PubMed |
description | Extensive departures from balanced gene dose in aneuploids are highly deleterious. However, we know very little about the relationship between gene copy number and expression in aneuploid cells. We determined copy number and transcript abundance (expression) genome-wide in Drosophila S2 cells by DNA-Seq and RNA-Seq. We found that S2 cells are aneuploid for >43 Mb of the genome, primarily in the range of one to five copies, and show a male genotype (∼ two X chromosomes and four sets of autosomes, or 2X;4A). Both X chromosomes and autosomes showed expression dosage compensation. X chromosome expression was elevated in a fixed-fold manner regardless of actual gene dose. In engineering terms, the system “anticipates” the perturbation caused by X dose, rather than responding to an error caused by the perturbation. This feed-forward regulation resulted in precise dosage compensation only when X dose was half of the autosome dose. Insufficient compensation occurred at lower X chromosome dose and excessive expression occurred at higher doses. RNAi knockdown of the Male Specific Lethal complex abolished feed-forward regulation. Both autosome and X chromosome genes show Male Specific Lethal–independent compensation that fits a first order dose-response curve. Our data indicate that expression dosage compensation dampens the effect of altered DNA copy number genome-wide. For the X chromosome, compensation includes fixed and dose-dependent components. |
format | Text |
id | pubmed-2826376 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-28263762010-02-26 Expression in Aneuploid Drosophila S2 Cells Zhang, Yu Malone, John H. Powell, Sara K. Periwal, Vipul Spana, Eric MacAlpine, David M. Oliver, Brian PLoS Biol Research Article Extensive departures from balanced gene dose in aneuploids are highly deleterious. However, we know very little about the relationship between gene copy number and expression in aneuploid cells. We determined copy number and transcript abundance (expression) genome-wide in Drosophila S2 cells by DNA-Seq and RNA-Seq. We found that S2 cells are aneuploid for >43 Mb of the genome, primarily in the range of one to five copies, and show a male genotype (∼ two X chromosomes and four sets of autosomes, or 2X;4A). Both X chromosomes and autosomes showed expression dosage compensation. X chromosome expression was elevated in a fixed-fold manner regardless of actual gene dose. In engineering terms, the system “anticipates” the perturbation caused by X dose, rather than responding to an error caused by the perturbation. This feed-forward regulation resulted in precise dosage compensation only when X dose was half of the autosome dose. Insufficient compensation occurred at lower X chromosome dose and excessive expression occurred at higher doses. RNAi knockdown of the Male Specific Lethal complex abolished feed-forward regulation. Both autosome and X chromosome genes show Male Specific Lethal–independent compensation that fits a first order dose-response curve. Our data indicate that expression dosage compensation dampens the effect of altered DNA copy number genome-wide. For the X chromosome, compensation includes fixed and dose-dependent components. Public Library of Science 2010-02-23 /pmc/articles/PMC2826376/ /pubmed/20186269 http://dx.doi.org/10.1371/journal.pbio.1000320 Text en This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Zhang, Yu Malone, John H. Powell, Sara K. Periwal, Vipul Spana, Eric MacAlpine, David M. Oliver, Brian Expression in Aneuploid Drosophila S2 Cells |
title | Expression in Aneuploid Drosophila S2 Cells |
title_full | Expression in Aneuploid Drosophila S2 Cells |
title_fullStr | Expression in Aneuploid Drosophila S2 Cells |
title_full_unstemmed | Expression in Aneuploid Drosophila S2 Cells |
title_short | Expression in Aneuploid Drosophila S2 Cells |
title_sort | expression in aneuploid drosophila s2 cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2826376/ https://www.ncbi.nlm.nih.gov/pubmed/20186269 http://dx.doi.org/10.1371/journal.pbio.1000320 |
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