Dido as a switchboard that regulates self-renewal and differentiation in embryonic stem cells (vsmut)

Transition from symmetric to asymmetric cell division requires precise coordination of differential gene expression. Embryonic stem cells (ESC) strongly express Dido3, whose C-terminal truncation impedes ESC differentiation while retaining self-renewal. We show that Dido3 binds to its gene locus via H3K4me3 and RNA pol II and, at differentiation onset, induces expression of its splice variant Dido1, which then leads to Dido3 degradation and downregulation of stemness genes. We propose that Dido isoforms act as a switchboard to regulate genetic programs for ESC transition from pluripotency maintenance to promotion of differentiation. We used microarrays to determine how the deletion of exon 16 (C-terminal truncation) of the Dido3 affects gene expression that results in the suppression of ESC differentiation. Mouse embryoid bodies from 2 conditions, wild type and truncated C-terminal Dido3 protein mutant, were cultured in pararell and equal conditions. After 10 days development, RNA was extracted and processed for hybridization on Agilent microarrays (Agilent Mouse GE 4x44K v2 Microarray). Three biological replicates for each condition were processed simultaneously.