---
_id: '14315'
abstract:
- lang: eng
  text: During apoptosis, caspases degrade 8 out of ~30 nucleoporins to irreversibly
    demolish the nuclear pore complex. However, for poorly understood reasons, caspases
    are also activated during cell differentiation. Here, we show that sublethal activation
    of caspases during myogenesis results in the transient proteolysis of four peripheral
    Nups and one transmembrane Nup. ‘Trimmed’ NPCs become nuclear export-defective,
    and we identified in an unbiased manner several classes of cytoplasmic, plasma
    membrane, and mitochondrial proteins that rapidly accumulate in the nucleus. NPC
    trimming by non-apoptotic caspases was also observed in neurogenesis and endoplasmic
    reticulum stress. Our results suggest that caspases can reversibly modulate nuclear
    transport activity, which allows them to function as agents of cell differentiation
    and adaptation at sublethal levels.
acknowledgement: 'We thank the members of the Hetzer laboratory, Tony Hunter (Salk),
  Lorenzo Puri (Sanford Burnham Prebys), and Jongmin Kim (Massachusetts General Hospital)
  for the critical reading of the manuscript; Kenneth Diffenderfer and Aimee Pankonin
  (Stem Cell Core at the Salk Institute) for help with neurogenesis; Carol Marchetto
  and Fred Gage (Salk) for providing H9 embryonic stem cells; Lorenzo Puri, Alexandra
  Sacco, and Luca Caputo (Sanford Burnham Prebys) for helpful discussions and sharing
  mouse primary myoblasts. This work was supported by a Glenn Foundation for Medical
  Research Postdoctoral Fellowship in Aging Research (UHC), the NOMIS foundation (MWH),
  and the National Institutes of Health (R01 NS096786 to MWH and K01 AR080828 to UHC).
  This work was also supported by the Mass Spectrometry Core of the Salk Institute
  with funding from NIH-NCI CCSG: P30 014195 and the Helmsley Center for Genomic Medicine.
  We thank Jolene Diedrich and Antonio Pinto for technical support.'
article_number: RP89066
article_processing_charge: Yes
article_type: original
author:
- first_name: Ukrae H.
  full_name: Cho, Ukrae H.
  last_name: Cho
- first_name: Martin W
  full_name: Hetzer, Martin W
  id: 86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed
  last_name: Hetzer
  orcid: 0000-0002-2111-992X
citation:
  ama: Cho UH, Hetzer M. Caspase-mediated nuclear pore complex trimming in cell differentiation
    and endoplasmic reticulum stress. <i>eLife</i>. 2023;12. doi:<a href="https://doi.org/10.7554/eLife.89066">10.7554/eLife.89066</a>
  apa: Cho, U. H., &#38; Hetzer, M. (2023). Caspase-mediated nuclear pore complex
    trimming in cell differentiation and endoplasmic reticulum stress. <i>ELife</i>.
    eLife Sciences Publications. <a href="https://doi.org/10.7554/eLife.89066">https://doi.org/10.7554/eLife.89066</a>
  chicago: Cho, Ukrae H., and Martin Hetzer. “Caspase-Mediated Nuclear Pore Complex
    Trimming in Cell Differentiation and Endoplasmic Reticulum Stress.” <i>ELife</i>.
    eLife Sciences Publications, 2023. <a href="https://doi.org/10.7554/eLife.89066">https://doi.org/10.7554/eLife.89066</a>.
  ieee: U. H. Cho and M. Hetzer, “Caspase-mediated nuclear pore complex trimming in
    cell differentiation and endoplasmic reticulum stress,” <i>eLife</i>, vol. 12.
    eLife Sciences Publications, 2023.
  ista: Cho UH, Hetzer M. 2023. Caspase-mediated nuclear pore complex trimming in
    cell differentiation and endoplasmic reticulum stress. eLife. 12, RP89066.
  mla: Cho, Ukrae H., and Martin Hetzer. “Caspase-Mediated Nuclear Pore Complex Trimming
    in Cell Differentiation and Endoplasmic Reticulum Stress.” <i>ELife</i>, vol.
    12, RP89066, eLife Sciences Publications, 2023, doi:<a href="https://doi.org/10.7554/eLife.89066">10.7554/eLife.89066</a>.
  short: U.H. Cho, M. Hetzer, ELife 12 (2023).
date_created: 2023-09-10T22:01:11Z
date_published: 2023-09-04T00:00:00Z
date_updated: 2023-09-15T07:07:10Z
day: '04'
ddc:
- '570'
department:
- _id: MaHe
doi: 10.7554/eLife.89066
external_id:
  pmid:
  - '37665327'
file:
- access_level: open_access
  checksum: db24bf3d595507387b48d3799c33e289
  content_type: application/pdf
  creator: dernst
  date_created: 2023-09-15T06:59:10Z
  date_updated: 2023-09-15T06:59:10Z
  file_id: '14336'
  file_name: 2023_eLife_Cho.pdf
  file_size: 3703097
  relation: main_file
  success: 1
file_date_updated: 2023-09-15T06:59:10Z
has_accepted_license: '1'
intvolume: '        12'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
publication: eLife
publication_identifier:
  eissn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Caspase-mediated nuclear pore complex trimming in cell differentiation and
  endoplasmic reticulum stress
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 12
year: '2023'
...
---
_id: '12880'
abstract:
- lang: eng
  text: Peripheral heterochromatin positioning depends on nuclear envelope associated
    proteins and repressive histone modifications. Here we show that overexpression
    (OE) of Lamin B1 (LmnB1) leads to the redistribution of peripheral heterochromatin
    into heterochromatic foci within the nucleoplasm. These changes represent a perturbation
    of heterochromatin binding at the nuclear periphery (NP) through a mechanism independent
    from altering other heterochromatin anchors or histone post-translational modifications.
    We further show that LmnB1 OE alters gene expression. These changes do not correlate
    with different levels of H3K9me3, but a significant number of the misregulated
    genes were likely mislocalized away from the NP upon LmnB1 OE. We also observed
    an enrichment of developmental processes amongst the upregulated genes. ~74% of
    these genes were normally repressed in our cell type, suggesting that LmnB1 OE
    promotes gene de-repression. This demonstrates a broader consequence of LmnB1
    OE on cell fate, and highlights the importance of maintaining proper levels of
    LmnB1.
acknowledgement: 'We thank members of the Hetzer lab for critical review of the manuscript;
  Novogene for mRNA library preparation and sequencing; the Next-Generation Sequencing
  Core Facility at the Salk Institute, with funding from NIH-NCI CCSG: P30 014195,
  the Chapman Foundation, and the Helmsley Charitable Trust, for sequencing Cut&Run
  libraries; and the Waitt Advanced Biophotonics Core Facility at the Salk Institute,
  with funding from NIH-NCI CCSG: P30 014195, the Waitt Foundation, and the Chan-Zuckerberg
  Initiative Imaging Scientist Award, for electron microscopy sample preparation and
  imaging.'
article_number: '2202548'
article_processing_charge: No
article_type: original
author:
- first_name: Jeanae M.
  full_name: Kaneshiro, Jeanae M.
  last_name: Kaneshiro
- first_name: Juliana S.
  full_name: Capitanio, Juliana S.
  last_name: Capitanio
- first_name: Martin W
  full_name: Hetzer, Martin W
  id: 86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed
  last_name: Hetzer
  orcid: 0000-0002-2111-992X
citation:
  ama: Kaneshiro JM, Capitanio JS, Hetzer M. Lamin B1 overexpression alters chromatin
    organization and gene expression. <i>Nucleus</i>. 2023;14(1). doi:<a href="https://doi.org/10.1080/19491034.2023.2202548">10.1080/19491034.2023.2202548</a>
  apa: Kaneshiro, J. M., Capitanio, J. S., &#38; Hetzer, M. (2023). Lamin B1 overexpression
    alters chromatin organization and gene expression. <i>Nucleus</i>. Taylor &#38;
    Francis. <a href="https://doi.org/10.1080/19491034.2023.2202548">https://doi.org/10.1080/19491034.2023.2202548</a>
  chicago: Kaneshiro, Jeanae M., Juliana S. Capitanio, and Martin Hetzer. “Lamin B1
    Overexpression Alters Chromatin Organization and Gene Expression.” <i>Nucleus</i>.
    Taylor &#38; Francis, 2023. <a href="https://doi.org/10.1080/19491034.2023.2202548">https://doi.org/10.1080/19491034.2023.2202548</a>.
  ieee: J. M. Kaneshiro, J. S. Capitanio, and M. Hetzer, “Lamin B1 overexpression
    alters chromatin organization and gene expression,” <i>Nucleus</i>, vol. 14, no.
    1. Taylor &#38; Francis, 2023.
  ista: Kaneshiro JM, Capitanio JS, Hetzer M. 2023. Lamin B1 overexpression alters
    chromatin organization and gene expression. Nucleus. 14(1), 2202548.
  mla: Kaneshiro, Jeanae M., et al. “Lamin B1 Overexpression Alters Chromatin Organization
    and Gene Expression.” <i>Nucleus</i>, vol. 14, no. 1, 2202548, Taylor &#38; Francis,
    2023, doi:<a href="https://doi.org/10.1080/19491034.2023.2202548">10.1080/19491034.2023.2202548</a>.
  short: J.M. Kaneshiro, J.S. Capitanio, M. Hetzer, Nucleus 14 (2023).
date_created: 2023-04-30T22:01:06Z
date_published: 2023-04-18T00:00:00Z
date_updated: 2023-08-01T14:18:46Z
day: '18'
ddc:
- '570'
department:
- _id: MaHe
doi: 10.1080/19491034.2023.2202548
external_id:
  isi:
  - '000971629400001'
  pmid:
  - '37071033'
file:
- access_level: open_access
  checksum: 8e707eda84f64dbad7f03545ae0a83ef
  content_type: application/pdf
  creator: dernst
  date_created: 2023-05-02T07:24:55Z
  date_updated: 2023-05-02T07:24:55Z
  file_id: '12884'
  file_name: 2023_Nucleus_Kaneshiro.pdf
  file_size: 3811113
  relation: main_file
  success: 1
file_date_updated: 2023-05-02T07:24:55Z
has_accepted_license: '1'
intvolume: '        14'
isi: 1
issue: '1'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc/4.0/
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
publication: Nucleus
publication_identifier:
  eissn:
  - 1949-1042
  issn:
  - 1949-1034
publication_status: published
publisher: Taylor & Francis
quality_controlled: '1'
scopus_import: '1'
status: public
title: Lamin B1 overexpression alters chromatin organization and gene expression
tmp:
  image: /images/cc_by_nc.png
  legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
  short: CC BY-NC (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 14
year: '2023'
...