Higher-order Chromatin Structure Controls T Helper Cell Differentiation

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The formation of higher-order chromatin structure composed of cis-regulatory elements including enhancers, silencers, and insulators play important roles in regulating cell lineage-specific activation and repression of genes. Cytokine genes expressed in T-helper cells are particularly attractive models to study lineage specific regulation by higher-order chromatin structure. In this study, we identified several cis-regulatory elements at the mouse IFN-g gene locus including IFN-g and IL-22. These elements functionally regulated lineage-specific gene expression as enhancers and silencers. Moreover, we try to generate mice with a conditional deletion of an insulator located 70 kb upstream of the IFN-g gene that is a site for recruitment of the factor CTCF, which may enable us to define the epigenetic and functional consequences of lineage-specific gene expression.