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Expression in aneuploid Drosophila S2 cells.
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 articleSubject
AneuploidyAnimals
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
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https://hdl.handle.net/10161/4445Published Version (Please cite this version)
10.1371/journal.pbio.1000320Publication 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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Show full item recordScholars@Duke
David 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 replicatio
Eric P. Spana
Associate Professor of the Practice of Biology
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