Embryonic stem cells (ESCs) are pluripotent stem cells from early embryos. It 
has been well recognized that ESC genomes are maintained in a globally 
transcriptional hyperactive state, which genetically poised ESCs to the high 
differentiation potential. However, the transcription factors regulating the 
global transcription activities in ESCs are not well defined. We show here that 
mouse and human ESCs express two transcription factors, Aire and Deaf1. 
Previously known to function in the thymus stromal cells and peripheral lymphoid 
organs respectively, Aire and Deaf1 help regulate the ectopic expression of 
diverse tissue-specific antigens to establish self-immune tolerance. 
Differentiation of ESCs greatly reduced Aire and Deaf1 expression, in a pattern 
similar to the pluripotent factors, Oct4 and Nanog. Knockdown of Aire in mouse 
ESCs resulted in significantly decreased clone-forming efficiency as well as 
attenuated cell cycle, suggesting Aire plays a role in ESC self-renewal. In 
addition, some differentiation-associated genes that are sporadically expressed 
in ESCs were reduced in expression upon Aire knockdown. These results suggest 
that transcription factors such as Aire and Deaf1, which exert global 
transcriptional regulatory functions, may play important roles in self-renewal 
of ESCs and maintaining ESC in a transcriptionally hyperactive state.