Dosage-Dependent Expression Variation Suppressed on the Drosophila Male X Chromosome.
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Authors
Lee, Hangnoh
Cho, Dong-Yeon
Wojtowicz, Damian
Harbison, Susan T
Publication Date
2018-02-02Journal Title
G3 (Bethesda)
ISSN
2160-1836
Publisher
Oxford University Press (OUP)
Volume
8
Issue
2
Pages
587-598
Language
eng
Type
Article
This Version
VoR
Physical Medium
Electronic
Metadata
Show full item recordCitation
Lee, H., Cho, D., Wojtowicz, D., Harbison, S. T., Russell, S., Oliver, B., & Przytycka, T. M. (2018). Dosage-Dependent Expression Variation Suppressed on the Drosophila Male X Chromosome.. G3 (Bethesda), 8 (2), 587-598. https://doi.org/10.1534/g3.117.300400
Abstract
DNA copy number variation is associated with many high phenotypic heterogeneity disorders. We systematically examined the impact of Drosophila melanogaster deletions on gene expression profiles to ask whether increased expression variability owing to reduced gene dose might underlie this phenotypic heterogeneity. Indeed, we found that one-dose genes have higher gene expression variability relative to two-dose genes. We then asked whether this increase in variability could be explained by intrinsic noise within cells due to stochastic biochemical events, or whether expression variability is due to extrinsic noise arising from more complex interactions. Our modeling showed that intrinsic gene expression noise averages at the organism level and thus cannot explain increased variation in one-dose gene expression. Interestingly, expression variability was related to the magnitude of expression compensation, suggesting that regulation, induced by gene dose reduction, is noisy. In a remarkable exception to this rule, the single X chromosome of males showed reduced expression variability, even compared with two-dose genes. Analysis of sex-transformed flies indicates that X expression variability is independent of the male differentiation program. Instead, we uncovered a correlation between occupancy of the chromatin-modifying protein encoded by males absent on the first (mof) and expression variability, linking noise suppression to the specialized X chromosome dosage compensation system. MOF occupancy on autosomes in both sexes also lowered transcriptional noise. Our results demonstrate that gene dose reduction can lead to heterogeneous responses, which are often noisy. This has implications for understanding gene network regulatory interactions and phenotypic heterogeneity. Additionally, chromatin modification appears to play a role in dampening transcriptional noise.
Keywords
X Chromosome, Chromatin, Animals, Drosophila melanogaster, Drosophila Proteins, Stochastic Processes, Gene Expression Profiling, Gene Dosage, Dosage Compensation, Genetic, Female, Male, DNA Copy Number Variations
Identifiers
External DOI: https://doi.org/10.1534/g3.117.300400
This record's URL: https://www.repository.cam.ac.uk/handle/1810/275082
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