ArticleThe Journal of biological chemistry2014
Histone cross-talk connects protein phosphatase 1α (PP1α) and histone deacetylase (HDAC) pathways to regulate the functional transition of bromodomain-containing 4 (BRD4) for inducible gene expression.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 45 citations in OpenAlex.
- Integrating Inflammatory and Epigenetic Signatures in IBD-Associated Colorectal Carcinogenesis: Models, Mechanisms, and Clinical Implications.International journal of molecular sciences · 2025Review
- Tailored therapies for triple-negative breast cancer: current landscape and future perceptions.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Targeting HECTD3-IKKα axis inhibits inflammation-related metastasis.Signal transduction and targeted therapy · 2022Article
- Disrupting the Cdk9/Cyclin T1 heterodimer of 7SK snRNP for the Brd4 and AFF1/4 guided reconstitution of active P-TEFb.Nucleic acids research · 2022Article
- Article
- Epigenetic Regulation of Inflammatory Signaling and Inflammation-Induced Cancer.Frontiers in cell and developmental biology · 2022Review
- The role of distinct BRD4 isoforms and their contribution to high-grade serous ovarian carcinoma pathogenesis.Molecular cancer · 2021Review
- Romidepsin (FK228) regulates the expression of the immune checkpoint ligand PD-L1 and suppresses cellular immune functions in colon cancer.Cancer immunology, immunotherapy : CII · 2021Article
- HDAC2 promotes the EMT of colorectal cancer cells and via the modular scaffold function of ENSG00000274093.1.Journal of cellular and molecular medicine · 2021Article
- Rebelled epigenome: histone H3S10 phosphorylation and H3S10 kinases in cancer biology and therapy.Clinical epigenetics · 2020Review
- Using Chemical Epigenetics to Target Cancer.Molecular cell · 2020Review
- Inhibition of BET Proteins and Histone Deacetylase (HDACs): Crossing Roads in Cancer Therapy.Cancers · 2019Review
- Enhancement of BDNF Expression and Memory by HDAC Inhibition Requires BET Bromodomain Reader Proteins.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- The Crosstalk between Acetylation and Phosphorylation: Emerging New Roles for HDAC Inhibitors in the Heart.International journal of molecular sciences · 2018Review
- HDAC stimulates gene expression through BRD4 availability in response to IFN and in interferonopathies.The Journal of experimental medicine · 2018Article
- A variant NuRD complex containing PWWP2A/B excludes MBD2/3 to regulate transcription at active genes.Nature communications · 2018Article
- The BET inhibitor INCB054329 reduces homologous recombination efficiency and augments PARP inhibitor activity in ovarian cancer.Gynecologic oncology · 2018Article
- P-TEFb: Finding its ways to release promoter-proximally paused RNA polymerase II.Transcription · 2018Review
- PP32 and SET/TAF-Iβ proteins regulate the acetylation of newly synthesized histone H4.Nucleic acids research · 2017Article
- Long non-coding RNA HoxA-AS3 interacts with EZH2 to regulate lineage commitment of mesenchymal stem cells.Oncotarget · 2016Article
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transcription elongation has been recognized as a rate-limiting step for the expression of signal-inducible genes. Through recruitment of positive transcription elongation factor P-TEFb, the bromodomain-containing protein BRD4 plays critical roles in regulating the transcription elongation of a vast array of inducible genes that are important for multiple cellular processes. The diverse biological roles of BRD4 have been proposed to rely on its functional transition between chromatin targeting and transcription regulation. The signaling pathways and the molecular mechanism for regulating this transition process, however, are largely unknown. Here, we report a novel role of phosphorylated Ser(10) of histone H3 (H3S10ph) in governing the functional transition of BRD4. We identified that the acetylated lysines 5 and 8 of nucleosomal histone H4 (H4K5ac/K8ac) is the BRD4 binding site, and the protein phosphatase PP1α and class I histone deacetylase (HDAC1/2/3) signaling pathways are essential for the stress-induced BRD4 release from chromatin. In the unstressed state, phosphorylated H3S10 prevents the deacetylation of nucleosomal H4K5ac/K8ac by HDAC1/2/3, thereby locking up the majority of BRD4 onto chromatin. Upon stress, PP1α-mediated dephosphorylation of H3S10ph allows the deacetylation of nucleosomal H4K5ac/K8ac by HDAC1/2/3, thereby leading to the release of chromatin-bound BRD4 for subsequent recruitment of P-TEFb to enhance the expression of inducible genes. Therefore, our study revealed a novel mechanism that the histone cross-talk between H3S10ph and H4K5ac/K8ac connects PP1α and HDACs to govern the functional transition of BRD4. Combined with previous studies on the regulation of P-TEFb activation, the intricate signaling network for the tight control of transcription elongation is established.
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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.