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Epigenetic and transcriptional signatures of stable versus plastic differentiation of proinflammatory ?? T cell subsets.

ABSTRACT: Two distinct subsets of ?? T cells that produce interleukin 17 (IL-17) (CD27(-) ?? T cells) or interferon-? (IFN-?) (CD27(+) ?? T cells) develop in the mouse thymus, but the molecular determinants of their functional potential in the periphery remain unknown. Here we conducted a genome-wide characterization of the methylation patterns of histone H3, along with analysis of mRNA encoding transcription factors, to identify the regulatory networks of peripheral IFN-?-producing or IL-17-producing ?? T cell subsets in vivo. We found that CD27(+) ?? T cells were committed to the expression of Ifng but not Il17, whereas CD27(-) ?? T cells displayed permissive chromatin configurations at loci encoding both cytokines and their regulatory transcription factors and differentiated into cells that produced both IL-17 and IFN-? in a tumor microenvironment.

SUBMITTER: Schmolka N

PROVIDER: S-EPMC4834994 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Epigenetic and transcriptional signatures of stable versus plastic differentiation of proinflammatory γδ T cell subsets.

Schmolka Nina N Serre Karine K Grosso Ana R AR Rei Margarida M Pennington Daniel J DJ Gomes Anita Q AQ Silva-Santos Bruno B

Nature immunology 20130901 10

Two distinct subsets of γδ T cells that produce interleukin 17 (IL-17) (CD27(-) γδ T cells) or interferon-γ (IFN-γ) (CD27(+) γδ T cells) develop in the mouse thymus, but the molecular determinants of their functional potential in the periphery remain unknown. Here we conducted a genome-wide characterization of the methylation patterns of histone H3, along with analysis of mRNA encoding transcription factors, to identify the regulatory networks of peripheral IFN-γ-producing or IL-17-producing γδ ...[more]

PMID: 23995235

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Project description:BACKGROUND: In all Metazoa, transcription is inactive during the first mitotic cycles after fertilisation. In Drosophila melanogaster, Zygotic Genome Activation (ZGA) occurs in two waves, starting respectively at mitotic cycles 8 (approximately 60 genes) and 14 (over a thousand genes). The regulatory mechanisms underlying these drastic transcriptional changes remain largely unknown. RESULTS: We developed an original gene clustering method based on discretized transition profiles, and applied it to datasets from three landmark early embryonic transcriptome studies. We identified 417 genes significantly up-regulated during ZGA. De novo?motif discovery returned nine motifs over-represented in their non-coding sequences (upstream, introns, UTR), three of which correspond to previously known transcription factors: Zelda, Tramtrack and Trithorax-like (Trl). The nine discovered motifs were combined to scan ZGA-associated regions and predict about 1300 putative cis-regulatory modules. The fact that Trl is known to act as chromatin remodelling factor suggests that epigenetic regulation might play an important role in zygotic genome activation. We thus systematically compared the locations of predicted CRMs with ChIP-seq profiles for various transcription factors, 38 epigenetic marks from ModENCODE, and DNAse1 accessibility profiles. This analysis highlighted a strong and specific enrichment of predicted ZGA-associated CRMs for Zelda, CBP, Trl binding sites, as well as for histone marks associated with active enhancers (H3K4me1) and for open chromatin regions. CONCLUSION: Based on the results of our computational analyses, we suggest a temporal model explaining the onset of zygotic genome activation by the combined action of transcription factors and epigenetic signals. Although this study is mainly based on the analysis of publicly available transcriptome and ChiP-seq datasets, the resulting model suggests novel mechanisms that underly the coordinated activation of several hundreds genes at a precise time point during embryonic development.

Dataset Information

Epigenetic and transcriptional signatures of stable versus plastic differentiation of proinflammatory ?? T cell subsets.

Publications

Epigenetic and transcriptional signatures of stable versus plastic differentiation of proinflammatory γδ T cell subsets.

Similar Datasets

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