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


Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
15 06 2021
Historique:
received: 23 07 2020
revised: 10 03 2021
accepted: 18 05 2021
entrez: 16 6 2021
pubmed: 17 6 2021
medline: 11 2 2022
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 34133927
pii: S2211-1247(21)00595-7
doi: 10.1016/j.celrep.2021.109236
pmc: PMC8224986
mid: NIHMS1715701
pii:
doi:

Substances chimiques

Drosophila Proteins 0
Histones 0
RNA, Messenger 0
TOR Serine-Threonine Kinases EC 2.7.11.1
Lysine K3Z4F929H6

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

109236

Subventions

Organisme : NIGMS NIH HHS
ID : R01 GM124143
Pays : United States
Organisme : NIGMS NIH HHS
ID : F31 GM133161
Pays : United States

Informations de copyright

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

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

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Auteurs

Jennifer R Aleman (JR)

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.

Terra M Kuhn (TM)

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.

Pau Pascual-Garcia (P)

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.

Janko Gospocic (J)

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.

Yemin Lan (Y)

Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Roberto Bonasio (R)

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.

Shawn C Little (SC)

Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Maya Capelson (M)

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: capelson@pennmedicine.upenn.edu.

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Classifications MeSH