Cited by 809Nuclear Structure and FunctionGenomics and Chromatin DynamicsSkin and Cellular Biology Research

LBR and lamin A/C sequentially tether peripheral heterochromatin and inversely regulate differentiation

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Solovei, Irina, Wang, Audrey S., Thanisch, Katharina, Schmidt, Christine S., Krebs, Stefan, Zwerger, Monika, Cohen, Tatiana V., Devys, Didier +8 more·2013·Cell

Abstract

Eukaryotic cells have a layer of heterochromatin at the nuclear periphery. To investigate mechanisms regulating chromatin distribution, we analyzed heterochromatin organization in different tissues and species, including mice with mutations in the lamin B receptor (Lbr) and lamin A (Lmna) genes that encode nuclear envelope (NE) proteins. We identified LBR- and lamin-A/C-dependent mechanisms tethering heterochromatin to the NE. The two tethers are sequentially used during cellular differentiation and development: first the LBR- and then the lamin-A/C-dependent tether. The absence of both LBR and lamin A/C leads to loss of peripheral heterochromatin and an inverted architecture with heterochromatin localizing to the nuclear interior. Myoblast transcriptome analyses indicated that selective disruption of the LBR- or lamin-A-dependent heterochromatin tethers have opposite effects on muscle gene expression, either increasing or decreasing, respectively. These results show how changes in NE composition contribute to regulating heterochromatin positioning, gene expression, and cellular differentiation during development.

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Crossref · 10.1016/j.cell.2013.01.009

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Authors
Solovei, I., Wang, A. S., Thanisch, K., Schmidt, C. S., Krebs, S., Zwerger, M., Cohen, T. V., Devys, D., Foisner, R., Peichl, L., Herrmann, H., Blum, H., Engelkamp, D., Stewart, C. L., Leonhardt, H., & Joffe, B.
Affiliations
  • Center for Integrated Protein Science Munich (DE)
  • National University of Singapore (SG)
  • Ludwig-Maximilians-Universität München (DE)
  • German Cancer Research Center (DE)
  • Children's National (US)
  • Centre National de la Recherche Scientifique (FR)
  • Max Perutz Labs (AT)
  • Max Planck Institute for Brain Research (DE)
  • Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
Corresponding author
  • Stewart, Colin L.
  • Leonhardt, Heinrich
  • Joffe, Boris
Venue
Cell
Publisher
Elsevier BV
Published
2013-01
Volume
152
Issue
3
Pages
584-598
ISSN
0092-8674 (ISSN-L)
OpenAlex
W1978992677
Cited by
809
References
58
Citations by year
2026: 41 · 2025: 57 · 2024: 48 · 2023: 44 · 2022: 64 · 2021: 85 · 2020: 76 · 2019: 75 · 2018: 70 · 2017: 59 · 2016: 60 · 2015: 52 · 2014: 46 · 2013: 32
FWCI
28.21
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Funders
  • Carnegie Institution for Science
  • Instytut Biologii Medycznej Polskiej Akademii Nauk
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
Keywords
lamin B receptor, lamin A/C, nuclear envelope, nuclear lamina, cell differentiation, myoblasts, muscle gene expression, chromatin organization, nuclear organization
MeSH terms
Lamin B Receptor, Animals, Heterochromatin, Nuclear Envelope, Receptors, Cytoplasmic and Nuclear, Gene Expression Profiling, Muscle Development, Myoblasts, Lamin Type A, Mice

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