CoChat
Sign Up
Cited by 236Nuclear Structure and FunctionDNA Repair MechanismsGenomics and Chromatin Dynamics

The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.

Histone H4 lysine 16 hypoacetylation is associated with defective DNA repair and premature senescence in Zmpste24-deficient mice

Open access
Krishnan, Vaidehi, Chow, Maggie Zi Ying, Wang, Zimei, Zhang, Le, Liu, Baohua, Liu, Xinguang, Zhou, Zhongjun·2011·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1102789108PMC PMC3145730
Open this paper in CoChat — free account

Abstract

Specific point mutations in lamin A gene have been shown to accelerate aging in humans and mice. Particularly, a de novo mutation at G608G position impairs lamin A processing to produce the mutant protein progerin, which causes the Hutchinson Gilford progeria syndrome. The premature aging phenotype of Hutchinson Gilford progeria syndrome is largely recapitulated in mice deficient for the lamin A-processing enzyme, Zmpste24. We have previously reported that Zmpste24 deficiency results in genomic instability and early cellular senescence due to the delayed recruitment of repair proteins to sites of DNA damage. Here, we further investigate the molecular mechanism underlying delayed DNA damage response and identify a histone acetylation defect in Zmpste24 −/− mice. Specifically, histone H4 was hypoacetylated at a lysine 16 residue (H4K16), and this defect was attributed to the reduced association of a histone acetyltransferase, Mof, to the nuclear matrix. Given the reversible nature of epigenetic changes, rescue experiments performed either by Mof overexpression or by histone deacetylase inhibition promoted repair protein recruitment to DNA damage sites and substantially ameliorated aging-associated phenotypes, both in vitro and in vivo. The life span of Zmpste24 −/− mice was also extended with the supplementation of a histone deacetylase inhibitor, sodium butyrate, to drinking water. Consistent with recent data showing age-dependent buildup of unprocessable lamin A in physiological aging, aged wild-type mice also showed hypoacetylation of H4K16. The above results shed light on how chromatin modifications regulate the DNA damage response and suggest that the reversal of epigenetic marks could make an attractive therapeutic target against laminopathy-based progeroid pathologies.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1073/pnas.1102789108

Cites

56 of 56 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 56 references

Cited by

Sorted by citations

Related

See all

Metadata

Authors
Krishnan, V., Chow, M. Z. Y., Wang, Z., Zhang, L., Liu, B., Liu, X., & Zhou, Z.
Affiliations
  • National University of Singapore (SG)
  • University of Hong Kong (HK)
  • Shenzhen University (CN)
  • Guangdong Medical College (CN)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2011-07-11
Volume
108
Issue
30
Pages
12325-12330
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1102789108
PMC
PMC3145730
OpenAlex
W2162996266
Cited by
236
References
56
Citations by year
2026: 13 · 2025: 8 · 2024: 12 · 2023: 8 · 2022: 11 · 2021: 15 · 2020: 19 · 2019: 15 · 2018: 21 · 2017: 11 · 2016: 20 · 2015: 21 · 2014: 18 · 2013: 19 · 2012: 22
FWCI
8.04
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • National University of Singapore (submittedVersion)
  • The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
Funders
  • National Natural Science Foundation of China (30871440, 30672205, 9252402301000002)
  • Natural Science Foundation of Guangdong Province (9252402301000002)
  • Innovation and Technology Fund
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
ZMPSTE24, Hutchinson-Gilford progeria syndrome, premature senescence, DNA repair, DNA damage response, histone deacetylase inhibition, sodium butyrate, laminopathies, premature aging, chromatin modification, nuclear matrix, genomic instability
MeSH terms
Tumor Suppressor p53-Binding Protein 1, Acetylation, Aging, Animals, Cells, Cultured, Chromosomal Proteins, Non-Histone, Disease Models, Animal, DNA Repair, DNA-Binding Proteins, Histones, Humans, Lysine, Membrane Proteins, Metalloendopeptidases, Nuclear Proteins, Protein Precursors, Nuclear Matrix, Cellular Senescence, Mice, Knockout, Aging, Premature, RNA, Small Interfering, Lamin Type A, Mice, Histone Acetyltransferases, Histone Deacetylase Inhibitors

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review