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Transcriptional and epigenetic regulation of T-helper lineage specification.

Tripathi SK, Lahesmaa R - Immunol. Rev. (2014)

Bottom Line: Combined with TCR stimuli, extracellular cytokine signals initiate the differentiation of naive CD4(+) T cells into specialized effector T-helper (Th) and regulatory T (Treg) cell subsets.The lineage specification and commitment process occurs through the combinatorial action of multiple transcription factors (TFs) and epigenetic mechanisms that drive lineage-specific gene expression programs.Moreover, we review current study linking immune disease-associated single-nucleotide polymorphisms with distal regulatory elements and their potential role in the disease etiology.

View Article: PubMed Central - PubMed

Affiliation: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland; National Doctoral Programme in Informational and Structural Biology, Turku, Finland; Turku Doctoral Programme of Molecular Medicine (TuDMM), University of Turku, Turku, Finland.

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Role of transcription factors in inducing the transcription of lineage-specific genes in T cells.Antigens and cytokines are extracellular signals received by T cells through T-cell receptors (TCRs)and cytokine receptors. Ligation of antigen to TCRs activate general acting pioneer transcriptionfactors (GPFs), such as NF-κB, NFAT, and AP-1 and cytokines binding to cognate cytokinereceptors lead to activation of environment response factors (ERFs), such as STATs. These pioneertranscription factors independently or synergistically regulate global chromatin state and theexpression of a lineage-specifying factor (LSF). LSFs and other co-factors further bind to thepre-existing chromatin landscape created by pioneer factors to regulate transcription of genesinvolved in lineage-specific gene expression program.
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fig02: Role of transcription factors in inducing the transcription of lineage-specific genes in T cells.Antigens and cytokines are extracellular signals received by T cells through T-cell receptors (TCRs)and cytokine receptors. Ligation of antigen to TCRs activate general acting pioneer transcriptionfactors (GPFs), such as NF-κB, NFAT, and AP-1 and cytokines binding to cognate cytokinereceptors lead to activation of environment response factors (ERFs), such as STATs. These pioneertranscription factors independently or synergistically regulate global chromatin state and theexpression of a lineage-specifying factor (LSF). LSFs and other co-factors further bind to thepre-existing chromatin landscape created by pioneer factors to regulate transcription of genesinvolved in lineage-specific gene expression program.

Mentions: We and others 76–79 have shown that the process of lineage specification and commitment of Th-cell lineagesis governed by their unique gene expression patterns. Each Th-cell lineage can be distinguished onthe basis of their unique transcriptional profiles. The lineage-specific transcriptional profilesare guided by the TFs that determine the fate of a specific T-cell lineage 23,80–84 (Fig. 2). TFs coordinatelineage-specific gene expression program by dictating the transcription of cell-specific genes thatdetermine the fate of a given Th-cell lineage and limit the development of other Th-cell lineages6,7,85. Several studies have documented the role of various TFs incontrolling the lineage specification and commitment program during the different stages of T-celldevelopment 86,87.


Transcriptional and epigenetic regulation of T-helper lineage specification.

Tripathi SK, Lahesmaa R - Immunol. Rev. (2014)

Role of transcription factors in inducing the transcription of lineage-specific genes in T cells.Antigens and cytokines are extracellular signals received by T cells through T-cell receptors (TCRs)and cytokine receptors. Ligation of antigen to TCRs activate general acting pioneer transcriptionfactors (GPFs), such as NF-κB, NFAT, and AP-1 and cytokines binding to cognate cytokinereceptors lead to activation of environment response factors (ERFs), such as STATs. These pioneertranscription factors independently or synergistically regulate global chromatin state and theexpression of a lineage-specifying factor (LSF). LSFs and other co-factors further bind to thepre-existing chromatin landscape created by pioneer factors to regulate transcription of genesinvolved in lineage-specific gene expression program.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4255756&req=5

fig02: Role of transcription factors in inducing the transcription of lineage-specific genes in T cells.Antigens and cytokines are extracellular signals received by T cells through T-cell receptors (TCRs)and cytokine receptors. Ligation of antigen to TCRs activate general acting pioneer transcriptionfactors (GPFs), such as NF-κB, NFAT, and AP-1 and cytokines binding to cognate cytokinereceptors lead to activation of environment response factors (ERFs), such as STATs. These pioneertranscription factors independently or synergistically regulate global chromatin state and theexpression of a lineage-specifying factor (LSF). LSFs and other co-factors further bind to thepre-existing chromatin landscape created by pioneer factors to regulate transcription of genesinvolved in lineage-specific gene expression program.
Mentions: We and others 76–79 have shown that the process of lineage specification and commitment of Th-cell lineagesis governed by their unique gene expression patterns. Each Th-cell lineage can be distinguished onthe basis of their unique transcriptional profiles. The lineage-specific transcriptional profilesare guided by the TFs that determine the fate of a specific T-cell lineage 23,80–84 (Fig. 2). TFs coordinatelineage-specific gene expression program by dictating the transcription of cell-specific genes thatdetermine the fate of a given Th-cell lineage and limit the development of other Th-cell lineages6,7,85. Several studies have documented the role of various TFs incontrolling the lineage specification and commitment program during the different stages of T-celldevelopment 86,87.

Bottom Line: Combined with TCR stimuli, extracellular cytokine signals initiate the differentiation of naive CD4(+) T cells into specialized effector T-helper (Th) and regulatory T (Treg) cell subsets.The lineage specification and commitment process occurs through the combinatorial action of multiple transcription factors (TFs) and epigenetic mechanisms that drive lineage-specific gene expression programs.Moreover, we review current study linking immune disease-associated single-nucleotide polymorphisms with distal regulatory elements and their potential role in the disease etiology.

View Article: PubMed Central - PubMed

Affiliation: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland; National Doctoral Programme in Informational and Structural Biology, Turku, Finland; Turku Doctoral Programme of Molecular Medicine (TuDMM), University of Turku, Turku, Finland.

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