In:
Nature Communications, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2016-05-23)
Kurzfassung:
T-cell development in the thymus is largely controlled by an epigenetic program, involving in both DNA methylation and histone modifications. Previous studies have identified Cxxc1 as a regulator of both cytosine methylation and histone 3 lysine 4 trimethylation (H3K4me3). However, it is unknown whether Cxxc1 plays a role in thymocyte development. Here we show that T-cell development in the thymus is severely impaired in Cxxc1 -deficient mice. Furthermore, we identify genome-wide Cxxc1-binding sites and H3K4me3 modification sites in wild-type and Cxxc1 -deficient thymocytes. Our results demonstrate that Cxxc1 directly controls the expression of key genes important for thymocyte survival such as RORγt and for T-cell receptor signalling including Zap70 and CD8, through maintaining the appropriate H3K4me3 on their promoters. Importantly, we show that RORγt, a direct target of Cxxc1, can rescue the survival defects in Cxxc1 -deficient thymocytes. Our data strongly support a critical role of Cxxc1 in thymocyte development.
Materialart:
Online-Ressource
ISSN:
2041-1723
Sprache:
Englisch
Verlag:
Springer Science and Business Media LLC
Publikationsdatum:
2016
ZDB Id:
2553671-0
