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Aleman JR, Kuhn TM, Pascual-Garcia P, et al. Correct dosage of X chromosome transcription is controlled by a nuclear pore component. Cell Rep. 2021;35(11):109236doi: 10.1016/j.celrep.2021.109236.
Aleman, J. R., Kuhn, T. M., Pascual-Garcia, P., Gospocic, J., Lan, Y., Bonasio, R., Little, S. C., & Capelson, M. (2021). Correct dosage of X chromosome transcription is controlled by a nuclear pore component. Cell reports, 35(11), 109236. https://doi.org/10.1016/j.celrep.2021.109236
Aleman, Jennifer R, et al. "Correct dosage of X chromosome transcription is controlled by a nuclear pore component." Cell reports vol. 35,11 (2021): 109236. doi: https://doi.org/10.1016/j.celrep.2021.109236
Aleman JR, Kuhn TM, Pascual-Garcia P, Gospocic J, Lan Y, Bonasio R, Little SC, Capelson M. Correct dosage of X chromosome transcription is controlled by a nuclear pore component. Cell Rep. 2021 Jun 15;35(11):109236. doi: 10.1016/j.celrep.2021.109236. PMID: 34133927; PMCID: PMC8224986.
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Cell Rep. 2021 Jun 15;35(11):109236. doi: 10.1016/j.celrep.2021.109236.

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

Cell reports

Jennifer R Aleman, Terra M Kuhn, Pau Pascual-Garcia, Janko Gospocic, Yemin Lan, Roberto Bonasio, Shawn C Little, Maya Capelson

Affiliations

  1. Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  2. Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Urology and Institute of Neuropathology, Medical Center-University of Freiburg, 79106 Freiburg, Germany.
  3. Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  4. Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  5. Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: [email protected].

PMID: 34133927 PMCID: PMC8224986 DOI: 10.1016/j.celrep.2021.109236

Abstract

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.

Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Keywords: MSL; Megator; Mtor; X chromosome; dosage compensation; nuclear pore complex; nucleoporin; transcription

Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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