摘要
Nanog is a transcription factor identified by its ability to maintain the self-renewal of ES cells in the absence of leukemia inhibitory factor (LIF). Nanog protein contains an N-terminal domain (ND), a DNA-binding homeobox domain (HD) and a C-terminal domain (CD). We previously reported that the CD in Nanog is a transcriptional activation domain essential for the in vivo function of Nanog. Here we demonstrated that the ND in Nanog is also functionally important. Deletion of the ND reduces the transcriptional activity of Nanog on either artificial reporters or native Nanog promoters. This truncated Nanog is also less effective in regulating the endogenous Nanog target genes. Furthermore, the ND truncation disrupted the ability of Nanog to maintain ES cell self-renewal as well. We found that the ND is not required for the nuclear localization of Nanog. These results suggest that the regulation of endogenous pluripotent genes such as oct3/4 and rex-1 is required for the in vivo function of Nanog.
Nanog is a transcription factor identified by its ability to maintain the self-renewal of ES cells in the absence of leukemia inhibitory factor （LIF）. Nanog protein contains an N-terminal domain （ND）, a DNA-binding homeobox domain （liD） and a C-terminal domain （CD）. We previously reported that the CD in Nanog is a transcriptional activation domain essential for the in vivo function of Nanog. liere we demonstrated that the ND in Nanog is also functionally important. Deletion of the ND reduces the transcriptional activity of Nanog on either artificial reporters or native Nanog promoters. This truncated Nanog is also less effective in regulating the endogenous Nanog target genes. Furthermore, the ND truncation disrupted the ability of Nanog to maintain ES cell self-renewal as well. We found that the ND is not required for the nuclear localization of Nanog. These results suggest that the regulation of endogenous pluripotent genes such as oct3/4 and rex-1 is required for the in vivo function of Nanog.
基金
Supported by the National Natural Science Foundation of China (Grant Nos. 30725012, 30630039 and 90813033)
Knowledge Innovation Project of Chinese Academy of Sciences (Grant No. KSCX2-YW-R-48)
Guangzhou Science and Technology Commission Foundation (Grant No. 2008A1-E4011)
National Key Basic Research and Development Program of China (Grant Nos. 2006CB701504, 2006CB943600, 2007CB948002 and 2007CB947804)
Beijing Forestry University Young Scientist Fund (Grant No. Blx2w8003)
