ArticleProceedings of the National Academy of Sciences of the United States of America2012
Target genes of Topoisomerase IIβ regulate neuronal survival and are defined by their chromatin state.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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Who cites it
96 citing papers in PubMed, 166 citations in OpenAlex.
- Analysis of gene expression changes upon topobexin treatment and TOP2B-knockout in hiPSC-derived cardiomyocytes.Biology open · 2026Article
- PDS5A and TOP2B cooperate for chromatin recruitment via CTCF.bioRxiv : the preprint server for biology · 2026Article
- The Roles of Topoisomerases in Transcriptional Regulation.International journal of molecular sciences · 2026Review
- TOP2B modulates DNA supercoiling and chromatin contacts during transcriptional induction.Science advances · 2025Article
- Reduction of DNA Topoisomerase Top2 Reprograms the Epigenetic Landscape and Extends Health and Life Span Across Species.Aging cell · 2025Article
- Reorganization of the heterochromatin-associated gene-dense subcompartment in early neuronal development.Biology open · 2025Article
- TOP2B is required for compartment strength changes upon retinoic acid treatment in SH-SY5Y cells.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2025Article
- How do neurons live long and healthy? The mechanism of neuronal genome integrity.Frontiers in neuroscience · 2025Review
- Topoisomerase-modulated genome-wide DNA supercoiling domains colocalize with nuclear compartments and regulate human gene expression.Nature structural & molecular biology · 2025Article
- UTX/Top2β axis mediated spinal cord microvascular endothelial cells senescence exacerbates spinal cord injury.PloS one · 2025Article
- Topoisomerase IIα-mediated stemness response in reactive astrocytes to traumatic brain injury.Theranostics · 2025Article
- Aclarubicin Reduces the Nuclear Mobility of Human DNA Topoisomerase IIβ.International journal of molecular sciences · 2024Article
- DNA topology: A central dynamic coordinator in chromatin regulation.Current opinion in structural biology · 2024Review
- Early oxidative stress and DNA damage in Aβ-burdened hippocampal neurons in an Alzheimer's-like transgenic rat model.Communications biology · 2024Article
- Gene regulatory landscape of cerebral cortex folding.Science advances · 2024Article
- Lipotype acquisition during neural development is not recapitulated in stem cell-derived neurons.Life science alliance · 2024Article
- A common molecular and cellular pathway in developing Alzheimer and cancer.Biochemistry and biophysics reports · 2024Review
- Mapping catalytically engaged TOP2B in neurons reveals the principles of topoisomerase action within the genome.Cell reports · 2024Article
- Topological regulation of the estrogen transcriptional response by ZATT-mediated inhibition of TOP2B activity.bioRxiv : the preprint server for biology · 2024Article
- Article
36 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Topoisomerases are essential for DNA replication in dividing cells, but their genomic targets and function in postmitotic cells remain poorly understood. Here we show that a switch in the expression from Topoisomerases IIα (Top2α) to IIβ (Top2β) occurs during neuronal differentiation in vitro and in vivo. Genome-scale location analysis in stem cell-derived postmitotic neurons reveals Top2β binding to chromosomal sites that are methylated at lysine 4 of histone H3, a feature of regulatory regions. Indeed Top2β-bound sites are preferentially promoters and become targets during the transition from neuronal progenitors to neurons, at a time when cells exit the cell cycle. Absence of Top2β protein or its activity leads to changes in transcription and chromatin accessibility at many target genes. Top2β deficiency does not impair stem cell properties and early steps of neuronal differentiation but causes premature death of postmitotic neurons. This neuronal degeneration is caused by up-regulation of Ngfr p75, a gene bound and repressed by Top2β. These findings suggest a chromatin-based targeting of Top2β to regulatory regions in the genome to govern the transcriptional program associated with neuronal differentiation and longevity.
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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.