LBR and lamin A/C sequentially tether peripheral heterochromatin and inversely regulate differentiation
Open accessAbstract
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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Lamin B1 plays a crucial role in 3D genome organization by tethering heterochromatin to the nuclear periphery.
“Lamin B1 plays a crucial role in the 3D genome organization by tethering heterochromatin to the nuclear periphery”
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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
- ORCID
- 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
- bronze
- doi.org
- Licence
- 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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