Effects of Gene Dose, Chromatin, and Network Topology on Expression in Drosophila melanogaster
Deletions, commonly referred to as deficiencies by Drosophila geneticists, are valuable tools for mapping genes and for genetic pathway discovery via dose-dependent suppressor and enhancer screens. More recently, it has become clear that deviations from normal gene dosage are associated with multipl...
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| Format: | Online |
| Language: | English |
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Public Library of Science
2016
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5012587/ |
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pubmed-5012587 |
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pubmed-50125872016-09-27 Effects of Gene Dose, Chromatin, and Network Topology on Expression in Drosophila melanogaster Lee, Hangnoh Cho, Dong-Yeon Whitworth, Cale Eisman, Robert Phelps, Melissa Roote, John Kaufman, Thomas Cook, Kevin Russell, Steven Przytycka, Teresa Oliver, Brian Research Article Deletions, commonly referred to as deficiencies by Drosophila geneticists, are valuable tools for mapping genes and for genetic pathway discovery via dose-dependent suppressor and enhancer screens. More recently, it has become clear that deviations from normal gene dosage are associated with multiple disorders in a range of species including humans. While we are beginning to understand some of the transcriptional effects brought about by gene dosage changes and the chromosome rearrangement breakpoints associated with them, much of this work relies on isolated examples. We have systematically examined deficiencies of the left arm of chromosome 2 and characterize gene-by-gene dosage responses that vary from collapsed expression through modest partial dosage compensation to full or even over compensation. We found negligible long-range effects of creating novel chromosome domains at deletion breakpoints, suggesting that cases of gene regulation due to altered nuclear architecture are rare. These rare cases include trans de-repression when deficiencies delete chromatin characterized as repressive in other studies. Generally, effects of breakpoints on expression are promoter proximal (~100bp) or in the gene body. Effects of deficiencies genome-wide are in genes with regulatory relationships to genes within the deleted segments, highlighting the subtle expression network defects in these sensitized genetic backgrounds. Public Library of Science 2016-09-06 /pmc/articles/PMC5012587/ /pubmed/27599372 http://dx.doi.org/10.1371/journal.pgen.1006295 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Lee, Hangnoh Cho, Dong-Yeon Whitworth, Cale Eisman, Robert Phelps, Melissa Roote, John Kaufman, Thomas Cook, Kevin Russell, Steven Przytycka, Teresa Oliver, Brian |
| spellingShingle |
Lee, Hangnoh Cho, Dong-Yeon Whitworth, Cale Eisman, Robert Phelps, Melissa Roote, John Kaufman, Thomas Cook, Kevin Russell, Steven Przytycka, Teresa Oliver, Brian Effects of Gene Dose, Chromatin, and Network Topology on Expression in Drosophila melanogaster |
| author_facet |
Lee, Hangnoh Cho, Dong-Yeon Whitworth, Cale Eisman, Robert Phelps, Melissa Roote, John Kaufman, Thomas Cook, Kevin Russell, Steven Przytycka, Teresa Oliver, Brian |
| author_sort |
Lee, Hangnoh |
| title |
Effects of Gene Dose, Chromatin, and Network Topology on Expression in Drosophila melanogaster |
| title_short |
Effects of Gene Dose, Chromatin, and Network Topology on Expression in Drosophila melanogaster |
| title_full |
Effects of Gene Dose, Chromatin, and Network Topology on Expression in Drosophila melanogaster |
| title_fullStr |
Effects of Gene Dose, Chromatin, and Network Topology on Expression in Drosophila melanogaster |
| title_full_unstemmed |
Effects of Gene Dose, Chromatin, and Network Topology on Expression in Drosophila melanogaster |
| title_sort |
effects of gene dose, chromatin, and network topology on expression in drosophila melanogaster |
| description |
Deletions, commonly referred to as deficiencies by Drosophila geneticists, are valuable tools for mapping genes and for genetic pathway discovery via dose-dependent suppressor and enhancer screens. More recently, it has become clear that deviations from normal gene dosage are associated with multiple disorders in a range of species including humans. While we are beginning to understand some of the transcriptional effects brought about by gene dosage changes and the chromosome rearrangement breakpoints associated with them, much of this work relies on isolated examples. We have systematically examined deficiencies of the left arm of chromosome 2 and characterize gene-by-gene dosage responses that vary from collapsed expression through modest partial dosage compensation to full or even over compensation. We found negligible long-range effects of creating novel chromosome domains at deletion breakpoints, suggesting that cases of gene regulation due to altered nuclear architecture are rare. These rare cases include trans de-repression when deficiencies delete chromatin characterized as repressive in other studies. Generally, effects of breakpoints on expression are promoter proximal (~100bp) or in the gene body. Effects of deficiencies genome-wide are in genes with regulatory relationships to genes within the deleted segments, highlighting the subtle expression network defects in these sensitized genetic backgrounds. |
| publisher |
Public Library of Science |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5012587/ |
| _version_ |
1613644253671456768 |