ArticleProceedings of the National Academy of Sciences of the United States of America2014
Histone deacetylase (HDAC) 1 and 2 are essential for accurate cell division and the pluripotency of embryonic stem cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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Who cites it
94 citing papers in PubMed, 166 citations in OpenAlex.
- Chemical Screening Identifies Danofloxacin as a Self-Renewal Agonist of Embryonic Stem Cells through Alleviation of HDAC1-Mediated Deacetylation of Tert and Prdm10.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Transient histone deacetylase inhibition induces cellular memory of gene expression and 3D genome folding.Nature genetics · 2026Article
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- The Allosteric Regulator Inositol Phosphate Dramatically Affects the Efficacy and Selectivity of Inhibitors for Different HDAC Complexes.Journal of the American Chemical Society · 2025Article
- Mutations on the surface of HDAC1 reveal molecular determinants of specific complex assembly and their requirement for gene regulation.Nucleic acids research · 2025Article
- Targeted Degradation of Class 1 HDACs With PROTACs is Highly Effective at Inducing DLBCL Cell Death.EJHaem · 2025Article
- CoREST in pieces: Dismantling the CoREST complex for cancer therapy and beyond.Science advances · 2025Review
- HDAC inhibitors modulate Hippo pathway signaling in hormone positive breast cancer.Clinical epigenetics · 2025Article
- Rapid degradation of histone deacetylase 1 (HDAC1) reveals essential roles in both gene repression and active transcription.Nucleic acids research · 2025Article
- Zscan4 mediates ubiquitination and degradation of the corepressor complex to promote chromatin accessibility in 2C-like cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Inhibition of HDAC8 mitigates AKI by reducing DNA damage and promoting homologous recombination repair.Journal of cellular and molecular medicine · 2024Article
- Novel Chitosan-Gelatin Scaffold with Valproic Acid Augments In Vitro Osteoblast Differentiation of Mesenchymal Stem Cells.Journal of functional biomaterials · 2024Article
- BET activity plays an essential role in control of stem cell attributes in Xenopus.Development (Cambridge, England) · 2024Article
- Dynamic Alterations in Acetylation and Modulation of Histone Deacetylase Expression Evident in the Dentine-Pulp Complex during Dentinogenesis.International journal of molecular sciences · 2024Article
- Histone Trimethylations and HDAC5 Regulate Spheroid Subpopulation and Differentiation Signaling of Human Adipose-Derived Stem Cells.Stem cells translational medicine · 2024Article
- Histone deacetylases maintain expression of the pluripotent gene network via recruitment of RNA polymerase II to coding and noncoding loci.Genome research · 2024Article
- A histone deacetylase network regulates epigenetic reprogramming and viral silencing in HIV-infected cells.Cell chemical biology · 2023Article
- A novel GRK3-HDAC2 regulatory pathway is a key direct link between neuroendocrine differentiation and angiogenesis in prostate cancer progression.Cancer letters · 2023Article
- Epigenetic and molecular coordination between HDAC2 and SMAD3-SKI regulates essential brain tumour stem cell characteristics.Nature communications · 2023Article
- Collateral lethality between HDAC1 and HDAC2 exploits cancer-specific NuRD complex vulnerabilities.Nature structural & molecular biology · 2023Article
34 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Histone deacetylases 1 and 2 (HDAC1/2) form the core catalytic components of corepressor complexes that modulate gene expression. In most cell types, deletion of both Hdac1 and Hdac2 is required to generate a discernible phenotype, suggesting their activity is largely redundant. We have therefore generated an ES cell line in which Hdac1 and Hdac2 can be inactivated simultaneously. Loss of HDAC1/2 resulted in a 60% reduction in total HDAC activity and a loss of cell viability. Cell death is dependent upon cell cycle progression, because differentiated, nonproliferating cells retain their viability. Furthermore, we observe increased mitotic defects, chromatin bridges, and micronuclei, suggesting HDAC1/2 are necessary for accurate chromosome segregation. Consistent with a critical role in the regulation of gene expression, microarray analysis of Hdac1/2-deleted cells reveals 1,708 differentially expressed genes. Significantly for the maintenance of stem cell self-renewal, we detected a reduction in the expression of the pluripotent transcription factors, Oct4, Nanog, Esrrb, and Rex1. HDAC1/2 activity is regulated through binding of an inositol tetraphosphate molecule (IP4) sandwiched between the HDAC and its cognate corepressor. This raises the important question of whether IP4 regulates the activity of the complex in cells. By rescuing the viability of double-knockout cells, we demonstrate for the first time (to our knowledge) that mutations that abolish IP4 binding reduce the activity of HDAC1/2 in vivo. Our data indicate that HDAC1/2 have essential and pleiotropic roles in cellular proliferation and regulate stem cell self-renewal by maintaining expression of key pluripotent transcription factors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.