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Reductive carboxylation epigenetically instructs T cell differentiation
Reductive carboxylation of glutamine by isocitrate dehydrogenase 2 (IDH2) has a role in determining the fate of T cells, and inhibiting this enzyme promotes the differentiation of memory T cells.
- Alison Jaccard
- , Tania Wyss
- & Mathias Wenes
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Ablation of cDC2 development by triple mutations within the Zeb2 enhancer
The transcription factor NFIL3 acts antagonistically to C/EBP proteins by binding the Zeb2 enhancer to prevent Zeb2 expression and the development of the conventional type 2 dendritic cell lineage.
- Tian-Tian Liu
- , Sunkyung Kim
- & Kenneth M. Murphy
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H1 histones control the epigenetic landscape by local chromatin compaction
Experiments using a conditional triple-knockout mouse strain show that histone H1 regulates the activity of chromatin domains by controlling chromatin compaction, genome architecture and histone methylation.
- Michael A. Willcockson
- , Sean E. Healton
- & Arthur I. Skoultchi
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Dichotomous engagement of HDAC3 activity governs inflammatory responses
During the activation of mouse macrophages by lipopolysaccharides, histone deacetylase 3 controls inflammatory responses by both repressing and activating gene transcription depending on its differential association with transcription factors.
- Hoang C. B. Nguyen
- , Marine Adlanmerini
- & Mitchell A. Lazar
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Article |
Histone H3.3 phosphorylation amplifies stimulation-induced transcription
The histone variant H3.3 is phosphorylated at Ser31 in induced genes, and this selective mark stimulates the histone methyltransferase SETD2 and ejects the ZMYND11 repressor, thus revealing a role for histone phosphorylation in amplifying de novo transcription.
- Anja Armache
- , Shuang Yang
- & Steven Z. Josefowicz
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Article |
TOX transcriptionally and epigenetically programs CD8+ T cell exhaustion
The transcription factor TOX is a central regulator of the transcriptional and epigenetic development of exhausted T cells.
- Omar Khan
- , Josephine R. Giles
- & E. John Wherry
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Letter |
Mitochondrial complex III is essential for suppressive function of regulatory T cells
Specific ablation of mitochondrial complex III subunits in Treg cells in mice results in inflammatory disease, altered Treg gene expression and defective Treg function, indicating a key functional role for mitochondrial complex III in Treg cells.
- Samuel E. Weinberg
- , Benjamin D. Singer
- & Navdeep S. Chandel
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Letter |
An epigenetic silencing pathway controlling T helper 2 cell lineage commitment
The histone modification H3K9me3, the histone methyltransferase SUV39H1 and the H3K9me3-binding protein HP1α participate in maintaining the silent state of the two canonical T helper 1 cell signature genes (which encode interferon-γ and T-bet), ensuring T helper 2 lineage stability in vitro and in vivo; targeting this pathway has the potential to reduce asthma-related pathology.
- Rhys S. Allan
- , Elina Zueva
- & Sebastian Amigorena
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Letter |
Generation of pathogenic TH17 cells in the absence of TGF-β signalling
CD4+ T cells that selectively produce interleukin (IL)-17 (TH17 cells) are essential for host defence and autoimmunity. It has been thought that IL-6 and transforming growth factor (TGF)-β1 are the factors responsible for initiating the specification of TH17 cells. Here, however, it is shown that TH17 differentiation can occur in the absence of TGF-β signalling. IL-6, IL-23 and IL-1β effectively induced IL-17 production in naive precursors. These data reveal an alternative mode for TH17 differentiation and the importance of IL-23.
- Kamran Ghoreschi
- , Arian Laurence
- & John J. O’Shea
Molecular basis for differential Igk versus Igh V(D)J joining mechanisms