ArticleNucleic acids research2018
Genome-wide dose-dependent inhibition of histone deacetylases studies reveal their roles in enhancer remodeling and suppression of oncogenic super-enhancers.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Mapping the Safety Profile of Histone Deacetylase Inhibitors in Children with Cancer.Clinical epigenetics · 2026Pooled it
- Selective histone deacetylase inhibition as a therapeutically relevant strategy in H3K27M-glioma.Neuro-oncology · 2026Article
- YAK577 Attenuates Vascular Calcification by Targeting an MMP14-NOX2/ROS Axis in VSMCs and a Vitamin DAntioxidants (Basel, Switzerland) · 2026Article
- HEXIM1/P-TEFb complex controls RNA polymerase II pause release and immediate early gene induction following neuronal depolarization.The Journal of biological chemistry · 2026Article
- MBD3 deficiency decommissions the nucleosome remodeling and deacetylase complex and orchestrates the epigenetic regulation of gene expression to suppress neuroblastoma progression.Neuro-oncology · 2026Article
- Largazole targets Musashi protein expression via miR-125b-5p and sensitizes triple-negative breast cancer cells to radiation.Frontiers in pharmacology · 2026Article
- Disruption of histone acetylation homeostasis reveals multilayered chromatin regulation for transcriptional resiliency.Epigenetics & chromatin · 2025Article
- Butyrate Selectively Targets Super-Enhancers and Transcriptional Networks Associated with Human Mast Cell Function.European journal of immunology · 2025Article
- Article
- Identification of molecular determinants of gene-specific bursting patterns by high-throughput imaging screens.Molecular cell · 2025Article
- Review
- Rapid degradation of histone deacetylase 1 (HDAC1) reveals essential roles in both gene repression and active transcription.Nucleic acids research · 2025Article
- Discovery of novel and potent dual-targeting AXL/HDAC2 inhibitors for colorectal cancer treatment via structure-based pharmacophore modelling, virtual screening, and molecular docking, molecular dynamics simulation studies, and biological evaluation.Journal of enzyme inhibition and medicinal chemistry · 2024Article
- Enhancers in T Cell development and malignant lesions.Cell death discovery · 2024Review
- Identification of molecular determinants of gene-specific bursting patterns by high-throughput imaging screens.bioRxiv : the preprint server for biology · 2024Article
- Histone deacetylases maintain expression of the pluripotent gene network via recruitment of RNA polymerase II to coding and noncoding loci.Genome research · 2024Article
- Sirtuin 2 inhibition modulates chromatin landscapes genome-wide to induce senescence in ATRX-deficient malignant glioma.Neuro-oncology · 2024Article
- Pathogenic role of super-enhancers as potential therapeutic targets in lung cancer.Frontiers in pharmacology · 2024Review
- High-capacity sample multiplexing for single cell chromatin accessibility profiling.BMC genomics · 2023Article
- The Roles of Histone Deacetylases in the Regulation of Ovarian Cancer Metastasis.International journal of molecular sciences · 2023Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors.
Funding
Abstract
Histone deacetylase inhibitors (HDACIs) are known to alter gene expression by both up- and down-regulation of protein-coding genes in normal and cancer cells. However, the exact regulatory mechanisms of action remain uncharacterized. Here we investigated genome wide dose-dependent epigenetic and transcriptome changes in response to HDACI largazole in a transformed and a non-transformed cell line. Exposure to low nanomolar largazole concentrations (<GI50) predominantly resulted in upregulation of gene transcripts whereas higher largazole doses (≥GI50) triggered a general decrease in mRNA accumulation. Largazole induces elevation of histone H3 acetylation at Lys-9 and Lys-27 along many gene bodies but does not correlate with up- or down-regulation of the associated transcripts. A higher dose of largazole results in more RNA polymerase II pausing at the promoters of actively transcribed genes and cell death. The most prevalent changes associated with transcriptional regulation occur at distal enhancer elements. Largazole promotes H3K27 acetylation at a subset of poised enhancers and unexpectedly, we also found active enhancers that become decommissioned in a dose and cell type-dependent manner. In particular, largazole decreases RNA polymerase II accumulation at super-enhancers (SEs) and preferentially suppresses SE-driven transcripts that are associated with oncogenic activities in transformed cells.
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