Expression in aneuploid Drosophila S2 cells.

dc.contributor.author

Zhang, Yu

dc.contributor.author

Malone, John H

dc.contributor.author

Powell, Sara K

dc.contributor.author

Periwal, Vipul

dc.contributor.author

Spana, Eric

dc.contributor.author

Macalpine, David M

dc.contributor.author

Oliver, Brian

dc.contributor.editor

Becker, Peter B

dc.coverage.spatial

United States

dc.date.accessioned

2011-06-21T17:31:06Z

dc.date.issued

2010-02-23

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.description.version

Version of Record

dc.identifier

http://www.ncbi.nlm.nih.gov/pubmed/20186269

dc.identifier.eissn

1545-7885

dc.identifier.uri

https://hdl.handle.net/10161/4445

dc.language

eng

dc.language.iso

en_US

dc.publisher

Public Library of Science (PLoS)

dc.relation.ispartof

PLoS Biol

dc.relation.isversionof

10.1371/journal.pbio.1000320

dc.relation.journal

Plos Biology

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
dc.type

Journal article

duke.contributor.orcid

Spana, Eric|0000-0002-2057-8278

duke.date.pubdate

2010-2-0

duke.description.issue

2

duke.description.volume

8

pubs.author-url

http://www.ncbi.nlm.nih.gov/pubmed/20186269

pubs.begin-page

e1000320

pubs.issue

2

pubs.organisational-group

Basic Science Departments

pubs.organisational-group

Biology

pubs.organisational-group

Duke

pubs.organisational-group

Duke Cancer Institute

pubs.organisational-group

Institutes and Centers

pubs.organisational-group

Pharmacology & Cancer Biology

pubs.organisational-group

School of Medicine

pubs.organisational-group

Trinity College of Arts & Sciences

pubs.publication-status

Published online

pubs.volume

8

Files

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
275257300010.pdf
Size:
1.75 MB
Format:
Adobe Portable Document Format