PUBLICATION

Nuclear Pores Regulate Muscle Development and Maintenance by Assembling a Localized Mef2C Complex

Authors
Raices, M., Bukata, L., Sakuma, S., Borlido, J., Hernandez, L.S., Hart, D.O., D'Angelo, M.A.
ID
ZDB-PUB-170913-8
Date
2017
Source
Developmental Cell   41: 540-554.e7 (Journal)
Registered Authors
D'angelo, Maximiliano
Keywords
MEF2C, Nup210, gene expression, genome organization, myofiber, myogenesis, nuclear envelope, nuclear periphery, nuclear pore complexes, sarcomere
MeSH Terms
  • Animals
  • Cell Differentiation
  • Cell Nucleus/genetics
  • Embryo, Nonmammalian/cytology*
  • Embryo, Nonmammalian/metabolism
  • MEF2 Transcription Factors/genetics
  • MEF2 Transcription Factors/metabolism*
  • Muscle Development/genetics*
  • Nuclear Envelope/genetics
  • Nuclear Pore/physiology*
  • Nuclear Pore Complex Proteins/genetics
  • Nuclear Pore Complex Proteins/metabolism*
  • Zebrafish/growth & development
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
28586646 Full text @ Dev. Cell
Abstract
Nuclear pore complexes (NPCs) are multiprotein channels connecting the nucleus with the cytoplasm. NPCs have been shown to have tissue-specific composition, suggesting that their function can be specialized. However, the physiological roles of NPC composition changes and their impacts on cellular processes remain unclear. Here we show that the addition of the Nup210 nucleoporin to NPCs during myoblast differentiation results in assembly of an Mef2C transcriptional complex required for efficient expression of muscle structural genes and microRNAs. We show that this NPC-localized complex is essential for muscle growth, myofiber maturation, and muscle cell survival and that alterations in its activity result in muscle degeneration. Our findings suggest that NPCs regulate the activity of functional gene groups by acting as scaffolds that promote the local assembly of tissue-specific transcription complexes and show how nuclear pore composition changes can be exploited to regulate gene expression at the nuclear periphery.
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Human Disease / Model
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Mapping