Correct dosage of X chromosome transcription is controlled by a nuclear pore component

Dosage compensation in Drosophila melanogaster involves a 2-fold transcriptional upregulation of the male X chromosome, which relies on the X-chromosome-binding males-specific lethal (MSL) complex. However, how such 2-fold precision is accomplished remains unclear. Here, we show that a nuclear pore...

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Bibliographic Details
Published inCell reports (Cambridge) Vol. 35; no. 11; p. 109236
Main Authors Aleman, Jennifer R, Kuhn, Terra M, Pascual-Garcia, Pau, Gospocic, Janko, Lan, Yemin, Bonasio, Roberto, Little, Shawn C, Capelson, Maya
Format Journal Article
LanguageEnglish
Published United States Elsevier 15.06.2021
Subjects
Acetylation
Animals
dosage compensation
Dosage Compensation, Genetic
Drosophila melanogaster - genetics
Drosophila Proteins - genetics
Drosophila Proteins - metabolism
Genes, Insect
Genes, X-Linked
Histones - metabolism
Lysine - metabolism
Male
Megator
Mtor
Nuclear Pore - genetics
nuclear pore complex
nucleoporin
RNA Transport - genetics
RNA, Messenger - genetics
RNA, Messenger - metabolism
TOR Serine-Threonine Kinases - metabolism
transcription
Transcription, Genetic
Up-Regulation - genetics
X Chromosome - genetics
transcription
MSL
Megator
X chromosome
nucleoporin
nuclear pore complex
Mtor
dosage compensation
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Summary:Dosage compensation in Drosophila melanogaster involves a 2-fold transcriptional upregulation of the male X chromosome, which relies on the X-chromosome-binding males-specific lethal (MSL) complex. However, how such 2-fold precision is accomplished remains unclear. Here, we show that a nuclear pore component, Mtor, is involved in setting the correct levels of transcription from the male X chromosome. Using larval tissues, we demonstrate that the depletion of Mtor results in selective upregulation at MSL targets of the male X, beyond the required 2-fold. Mtor and MSL components interact genetically, and depletion of Mtor can rescue the male lethality phenotype of MSL components. Using RNA fluorescence in situ hybridization (FISH) analysis and nascent transcript sequencing, we find that the effect of Mtor is not due to defects in mRNA export but occurs at the level of nascent transcription. These findings demonstrate a physiological role for Mtor in the process of dosage compensation, as a transcriptional attenuator of X chromosome gene expression.
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AUTHOR CONTRIBUTIONS
J.R.A. and M.C. designed, interpreted the experiments, and wrote the manuscript. T.M.K. carried out the TT-seq experiments. J.G. and R.B. contributed technical assistance for the RNA-seq and TT-seq experiments and intellectually with their interpretations of the genetic and sequencing experiments. P.P.-G. carried out the biochemical characterization of H4K16ac and ChIP-qPCR experiments. S.C.L. contributed to the smRNA FISH experiments and performed the image analysis. J.R.A. performed all of the other experiments. Y.L. provided the bioinformatics analysis.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2021.109236