ArticlePLoS genetics2014
Deletion of a conserved cis-element in the Ifng locus highlights the role of acute histone acetylation in modulating inducible gene transcription.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- Epigenetic mechanisms of inflammatory memory in the central nervous system.Nature immunology · 2026Review
- Regulation of T helper cell differentiation by the interplay between histone modification and chromatin interaction.Immunity · 2024Article
- Restraint of IFN-γ expression through a distal silencer CNS-28 for tissue homeostasis.Immunity · 2023Article
- Small Molecule Inhibitors Targeting Nuclear Factor κB Activation Markedly Reduce Expression of Interleukin-2, but Not Interferon-γ, Induced by Phorbol Esters and Calcium Ionophores.International journal of molecular sciences · 2021Article
- In search of lost time: Enhancers as modulators of timing in lymphocyte development and differentiation.Immunological reviews · 2021Review
- Comprehensive construction strategy of bidirectional green tissue-specific synthetic promoters.Plant biotechnology journal · 2020Article
- NCOR1 Orchestrates Transcriptional Landscapes and Effector Functions of CD4Frontiers in immunology · 2020Article
- Genome-wide cis-regulatory signatures for modulation of agronomic traits as exemplified by drought yield index (DYI) in chickpea.Functional & integrative genomics · 2019Article
- Dust mite allergen-specific immunotherapy increases IL4 DNA methylation and induces Der p-specific T cell tolerance in children with allergic asthma.Cellular & molecular immunology · 2018Article
- Article
- Isolation and Functional Characterization of Bidirectional Promoters in Rice.Frontiers in plant science · 2016Article
- Novel green tissue-specific synthetic promoters and cis-regulatory elements in rice.Scientific reports · 2015Article
- Functional validation of mouse tyrosinase non-coding regulatory DNA elements by CRISPR-Cas9-mediated mutagenesis.Nucleic acids research · 2015Article
- Transcriptional Enhancers in the Regulation of T Cell Differentiation.Frontiers in immunology · 2015Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Differentiation-dependent regulation of the Ifng cytokine gene locus in T helper (Th) cells has emerged as an excellent model for functional study of distal elements that control lineage-specific gene expression. We previously identified a cis-regulatory element located 22 kb upstream of the Ifng gene (Conserved Non-coding Sequence -22, or CNS-22) that is a site for recruitment of the transcription factors T-bet, Runx3, NF-κB and STAT4, which act to regulate transcription of the Ifng gene in Th1 cells. Here, we report the generation of mice with a conditional deletion of CNS-22 that has enabled us to define the epigenetic and functional consequences of its absence. Deletion of CNS-22 led to a defect in induction of Ifng by the cytokines IL-12 and IL-18, with a more modest effect on induction via T-cell receptor activation. To better understand how CNS-22 and other Ifng CNSs regulated Ifng transcription in response to these distinct stimuli, we examined activation-dependent changes in epigenetic modifications across the extended Ifng locus in CNS-22-deficient T cells. We demonstrate that in response to both cytokine and TCR driven activation signals, CNS-22 and other Ifng CNSs recruit increased activity of histone acetyl transferases (HATs) that transiently enhance levels of histones H3 and H4 acetylation across the extended Ifng locus. We also demonstrate that activation-responsive increases in histone acetylation levels are directly linked to the ability of Ifng CNSs to acutely enhance Pol II recruitment to the Ifng promoter. Finally, we show that impairment in IL-12+IL-18 dependent induction of Ifng stems from the importance of CNS-22 in coordinating locus-wide levels of histone acetylation in response to these cytokines. These findings identify a role for acute histone acetylation in the enhancer function of distal conserved cis-elements that regulate of Ifng gene expression.
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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.