ArticleCirculation. Heart failure2015
Acute targeting of general transcription factor IIB restricts cardiac hypertrophy via selective inhibition of gene transcription.
Article in Circulation. Heart failure, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- Genomic analyses implicate noncoding de novo variants in congenital heart disease.Nature genetics · 2020Trial
- ReDisulphID: A discovery platform for thiol redox sensors identifies a druggable site regulating p53 activation.Redox biology · 2026Article
- Constitutive expression of cardiomyocyte Klf9 precipitates metabolic dysfunction and spontaneous cardiomyopathy.Cellular signalling · 2025Article
- The general transcription factors (GTFs) of RNA polymerase II and their roles in plant development and stress responses.Critical reviews in biochemistry and molecular biology · 2024Review
- Reducing branched-chain amino acids improves cardiac stress response in mice by decreasing histone H3K23 propionylation.The Journal of clinical investigation · 2023Article
- Klf9 plays a critical role in GR -dependent metabolic adaptations in cardiomyocytes.Cellular signalling · 2023Article
- G3bp1 - microRNA-1 axis regulates cardiomyocyte hypertrophy.Cellular signalling · 2022Article
- Taking Data Science to Heart: Next Scale of Gene Regulation.Current cardiology reports · 2021Review
- Genomic Binding Patterns of Forkhead Box Protein O1 Reveal Its Unique Role in Cardiac Hypertrophy.Circulation · 2020Article
- Acute NelfA knockdown restricts compensatory gene expression and precipitates ventricular dysfunction during cardiac hypertrophy.Journal of molecular and cellular cardiology · 2020Article
- Oxoglutarate dehydrogenase and acetyl-CoA acyltransferase 2 selectively associate with H2A.Z-occupied promoters and are required for histone modifications.Biochimica et biophysica acta. Gene regulatory mechanisms · 2019Article
- Epigenetic therapies in heart failure.Journal of molecular and cellular cardiology · 2019Article
- Glucocorticoid Receptor-Binding and Transcriptome Signature in Cardiomyocytes.Journal of the American Heart Association · 2019Article
- Direct visualization of cardiac transcription factories reveals regulatory principles of nuclear architecture during pathological remodeling.Journal of molecular and cellular cardiology · 2019Article
- Transcriptional regulation mediated by H2A.Z via ANP32e-dependent inhibition of protein phosphatase 2A.Biochimica et biophysica acta. Gene regulatory mechanisms · 2018Article
- Viral targeting of TFIIB impairs de novo polymerase II recruitment and affects antiviral immunity.PLoS pathogens · 2018Article
- Gene expression analysis to identify mechanisms underlying heart failure susceptibility in mice and humans.Basic research in cardiology · 2018Article
- Btg2 is a Negative Regulator of Cardiomyocyte Hypertrophy through a Decrease in Cytosolic RNA.Scientific reports · 2016Article
- Cardiac Disease Status Dictates Functional mRNA Targeting Profiles of Individual MicroRNAs.Circulation. Cardiovascular genetics · 2015Article
- GTPase Activating Protein (Sh3 Domain) Binding Protein 1 Regulates the Processing of MicroRNA-1 during Cardiac Hypertrophy.PloS one · 2015Article
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Authors and funding
5 authors at 1 institution in 1 country.
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Abstract
backgroundWe previously reported that specialized and housekeeping genes are differentially regulated via de novo recruitment and pause-release of RNA polymerase II, respectively, during cardiac hypertrophy. However, the significance of this finding remains to be examined. Therefore, the purpose of this study was to determine the mechanisms that differentially regulate these gene groups and exploit them for therapeutic targeting. METHODS AND
resultsHere, we show that general transcription factor IIB (TFIIB) and cyclin-dependent kinase 9 are upregulated during hypertrophy, both targeted by microRNA-1, and play preferential roles in regulating those 2 groups of genes. Chromatin immunoprecipitation-sequencing reveals that TFIIB is constitutively bound to all paused, housekeeping, promoters, whereas de novo recruitment of TFIIB and polymerase II is required for specialized genes that are induced during hypertrophy. We exploited this dichotomy to acutely inhibit induction of the latter set, which encompasses cardiomyopathy, immune reaction, and extracellular matrix genes, using locked nucleic acid-modified antisense TFIIB oligonucleotide treatment. This resulted in suppression of all specialized genes, while sparing the housekeeping ones, and, thus, attenuated pathological hypertrophy.
conclusionsThe data for the first time reveal distinct general TFIIB dynamics that regulate specialized versus housekeeping genes during cardiac hypertrophy. Thus, by acutely targeting TFIIB, we were able to inhibit selectively the former set of genes and ameliorate pressure overload hypertrophy. We also demonstrate the feasibility of acutely and reversibly targeting cardiac mRNA for therapeutic purposes using locked nucleic acid-modified antisense oligonucleotides.
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