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dc.contributor.author Zhang, Y
dc.contributor.author Malone, JH
dc.contributor.author Powell, SK
dc.contributor.author Periwal, V
dc.contributor.author Spana, E
dc.contributor.author Macalpine, DM
dc.contributor.author Oliver, B
dc.coverage.spatial United States
dc.date.accessioned 2011-06-21T17:31:06Z
dc.date.issued 2010-02-23
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/20186269
dc.identifier.citation PLoS Biol, 2010, 8 (2), pp. e1000320 - ?
dc.identifier.uri http://hdl.handle.net/10161/4445
dc.description.abstract 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 ( approximately 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.
dc.format.extent e1000320 - ?
dc.language ENG
dc.language.iso en_US en_US
dc.relation.ispartof PLoS Biol
dc.relation.isversionof 10.1371/journal.pbio.1000320
dc.subject Aneuploidy
dc.subject Animals
dc.subject Blotting, Western
dc.subject Cell Line
dc.subject Chromatin Immunoprecipitation
dc.subject Comparative Genomic Hybridization
dc.subject Dosage Compensation, Genetic
dc.subject Drosophila
dc.subject Drosophila Proteins
dc.subject Gene Expression Regulation
dc.subject Male
dc.subject Oligonucleotide Array Sequence Analysis
dc.subject RNA Interference
dc.subject Sequence Analysis, DNA
dc.subject X Chromosome
dc.title Expression in aneuploid Drosophila S2 cells.
dc.title.alternative en_US
dc.type Journal Article
dc.description.version Version of Record en_US
duke.date.pubdate 2010-2-0 en_US
duke.description.endpage e1000320 en_US
duke.description.issue 2 en_US
duke.description.startpage e1000320 en_US
duke.description.volume 8 en_US
dc.relation.journal Plos Biology en_US
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/20186269
pubs.issue 2
pubs.organisational-group /Duke
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Pharmacology & Cancer Biology
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Cancer Institute
pubs.organisational-group /Duke/Trinity College of Arts & Sciences
pubs.organisational-group /Duke/Trinity College of Arts & Sciences/Biology
pubs.publication-status Published online
pubs.volume 8
dc.identifier.eissn 1545-7885

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