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Transcriptional program of Kpna2/Importin-α2 regulates cellular differentiation-coupled circadian clock development in mammalian cells.


ABSTRACT: The circadian clock in mammalian cells is cell-autonomously generated during the cellular differentiation process, but the underlying mechanisms are not understood. Here we show that perturbation of the transcriptional program by constitutive expression of transcription factor c-Myc and DNA methyltransferase 1 (Dnmt1) ablation disrupts the differentiation-coupled emergence of the clock from mouse ESCs. Using these model ESCs, 484 genes are identified by global gene expression analysis as factors correlated with differentiation-coupled circadian clock development. Among them, we find the misregulation of Kpna2 (Importin-α2) during the differentiation of the c-Myc-overexpressed and Dnmt1(-/-) ESCs, in which sustained cytoplasmic accumulation of PER proteins is observed. Moreover, constitutiv

SUBMITTER: Umemura Y 

PROVIDER: S-EPMC4250115 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature