Aire regulates the expression of differentiation-associated genes and self-renewal of embryonic stem cells.
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.
Gu
Bin
B
The Institute of Cell Biology and Genetics, College of Life Sciences, Zhejiang University, 388 Yuhangtang Road, Hangzhou, China.
Zhang
Jiarong
J
Chen
Qi
Q
Tao
Bo
B
Wang
Wei
W
Zhou
Yang
Y
Chen
Liangbiao
L
Liu
Yusen
Y
Zhang
Ming
M
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D004268:DNA-Binding Proteins; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000502:physiology*; D005453:Fluorescence; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000096927:AIRE Protein
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D000096927:AIRE Protein; C116013:DEAF1 protein, human; C548809:Deaf1 protein, mouse