PMID- 34133927
OWN - NLM
STAT- MEDLINE
DCOM- 20220210
LR  - 20240505
IS  - 2211-1247 (Electronic)
VI  - 35
IP  - 11
DP  - 2021 Jun 15
TI  - Correct dosage of X chromosome transcription is controlled by a nuclear pore 
      component.
PG  - 109236
LID - S2211-1247(21)00595-7 [pii]
LID - 10.1016/j.celrep.2021.109236 [doi]
AB  - 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.
CI  - Copyright (c) 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Aleman, Jennifer R
AU  - Aleman JR
AD  - 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.
FAU - Kuhn, Terra M
AU  - Kuhn TM
AD  - 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.
FAU - Pascual-Garcia, Pau
AU  - Pascual-Garcia P
AD  - 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.
FAU - Gospocic, Janko
AU  - Gospocic J
AD  - 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.
FAU - Lan, Yemin
AU  - Lan Y
AD  - Penn Epigenetics Institute, Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia, PA 19104, USA.
FAU - Bonasio, Roberto
AU  - Bonasio R
AD  - 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.
FAU - Little, Shawn C
AU  - Little SC
AD  - Department of Cell and Developmental Biology, Perelman School of Medicine, 
      University of Pennsylvania, Philadelphia, PA 19104, USA.
FAU - Capelson, Maya
AU  - Capelson M
AD  - 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.
LA  - eng
GR  - F31 GM133161/GM/NIGMS NIH HHS/United States
GR  - R01 GM124143/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Drosophila Proteins)
RN  - 0 (Histones)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Acetylation
MH  - Animals
MH  - *Dosage Compensation, Genetic
MH  - Drosophila Proteins/genetics/metabolism
MH  - Drosophila melanogaster/*genetics
MH  - Genes, Insect
MH  - Genes, X-Linked
MH  - Histones/metabolism
MH  - Lysine/metabolism
MH  - Male
MH  - Nuclear Pore/*genetics
MH  - RNA Transport/genetics
MH  - RNA, Messenger/genetics/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - *Transcription, Genetic
MH  - Up-Regulation/genetics
MH  - X Chromosome/*genetics
PMC - PMC8224986
MID - NIHMS1715701
OTO - NOTNLM
OT  - MSL
OT  - Megator
OT  - Mtor
OT  - X chromosome
OT  - dosage compensation
OT  - nuclear pore complex
OT  - nucleoporin
OT  - transcription
COIS- Declaration of interests The authors declare no competing interests.
EDAT- 2021/06/17 06:00
MHDA- 2022/02/11 06:00
PMCR- 2021/06/24
CRDT- 2021/06/16 20:07
PHST- 2020/07/23 00:00 [received]
PHST- 2021/03/10 00:00 [revised]
PHST- 2021/05/18 00:00 [accepted]
PHST- 2021/06/16 20:07 [entrez]
PHST- 2021/06/17 06:00 [pubmed]
PHST- 2022/02/11 06:00 [medline]
PHST- 2021/06/24 00:00 [pmc-release]
AID - S2211-1247(21)00595-7 [pii]
AID - 10.1016/j.celrep.2021.109236 [doi]
PST - ppublish
SO  - Cell Rep. 2021 Jun 15;35(11):109236. doi: 10.1016/j.celrep.2021.109236.