Transcriptional and epigenetic regulation of T-helper lineage specification.
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.
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.Show MeSH
Mentions: Epigenetic mechanisms also regulate gene expression programs. Epigenetic factors control theaccessibility of TFs to their cognate cis-regulatory regions within the highlyordered chromatin structure 14,25–27. Specific TFs recruit chromatinremodeling complexes to specific regulatory regions which then participate in gene regulationthrough their enzymatic or nucleosome remodeling activities 28,29. DNA methylation, posttranslationalmodification of histone tails, chromatin remodeling complexes, chromatin interaction/chromosomeconfirmation, and non-coding RNAs (ncRNAs) are the major epigenetic factors that participate in thegene regulation by either activating or repressing gene expression programs 29–32. The epigenetic modificationsassociated with active chromatin state open the tightly packed chromatin structure and exposecis-regulatory elements available for the binding of TFs and other regulatoryDNA-binding proteins to activate gene expression and vice versa for the epigenetic modificationsassociated with repressive chromatin structure (Fig. 1). It has been shown that these epigenetic modifications are generated anderased in a precise fashion during the course of differentiation and development of various cellsand tissues, and are altered in response to intrinsic and extrinsic stimulus.
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.