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Expression in aneuploid Drosophila S2 cells.

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Date
2010-02-23
Authors
Zhang, Yu
Malone, John H
Powell, Sara K
Periwal, Vipul
Spana, Eric
Macalpine, David M
Oliver, Brian
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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.
Type
Journal article
Subject
Aneuploidy
Animals
Blotting, Western
Cell Line
Chromatin Immunoprecipitation
Comparative Genomic Hybridization
Dosage Compensation, Genetic
Drosophila
Drosophila Proteins
Gene Expression Regulation
Male
Oligonucleotide Array Sequence Analysis
RNA Interference
Sequence Analysis, DNA
X Chromosome
Permalink
https://hdl.handle.net/10161/4445
Published Version (Please cite this version)
10.1371/journal.pbio.1000320
Publication Info
Zhang, Yu; Malone, John H; Powell, Sara K; Periwal, Vipul; Spana, Eric; Macalpine, David M; & Oliver, Brian (2010). Expression in aneuploid Drosophila S2 cells. PLoS Biol, 8(2). pp. e1000320. 10.1371/journal.pbio.1000320. Retrieved from https://hdl.handle.net/10161/4445.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

MacAlpine

David Michael MacAlpine

Professor of Pharmacology and Cancer Biology
Our laboratory is interested in understanding the mechanisms by which the molecular architecture of the chromosome regulates fundamental biological processes such as replication and transcription. Specifically, how are replication, transcription and chromatin modification coordinated on a genomic scale to maintain genomic stability? We are addressing this question by using genomic, computational and biochemical approaches in the model organism Drosophila melanogaster. DNA replica
Spana

Eric P. Spana

Associate Professor of the Practice of Biology
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