T-Helper Polarization: Regulation by Noncoding RNA and Super-Enhancers

Abstract

Naïve CD4+ T cells polarize into many varied CD4+ T-helper (TH) cell subsets depending on the cytokine milieu present during T cell receptor stimulation. Each T cell subset produces a unique cytokine profile to defend against varied pathogens. The polarization of each T cell subset is regulated by unique transcription factors and noncoding elements to induce cytokine expression. The research detailed identifies a noncoding RNA, GATA3-AS1, which is necessary for the expression of GATA3 and TH2 cell polarization. Furthermore, we describe the repression of IFN-γ by super-enhancer disruption via bromodomain inhibitor JQ1. Our results lend novel insight into the regulation of hallmark genes by noncoding elements in T-helper cell polarization.