The Sox-2 regulatory regions display their activities in two distinct types of multipotent stem cells.
The Sox-2 gene is expressed in embryonic stem (ES) cells and neural stem cells. Two transcription enhancer regions, Sox-2 regulatory region 1 (SRR1) and SRR2, were described previously based on their activities in ES cells. Here, we demonstrate that these regulatory regions also exert their activities in neural stem cells. Moreover, our data reveal that, as in ES cells, both SRR1 and SRR2 show their activities rather specifically in multipotent neural stem or progenitor cells but cease to function in differentiated cells, such as postmitotic neurons. Systematic deletion and mutation analyses showed that the same or at least overlapping DNA elements of SRR2 are involved in its activity in both ES and neural stem or progenitor cells. Thus, SRR2 is the first example of an enhancer in which a single regulatory core sequence is involved in multipotent-state-specific expression in two different stem cells, i.e., ES and neural stem cells.
Miyagi
Satoru
S
Division of Developmental Biology, Research Center for Genomic Medicine, Saitama Medical School, Saitama 350-1241, Japan.
Saito
Tetsuichiro
T
Mizutani
Ken-ichi
K
Masuyama
Norihisa
N
Gotoh
Yukiko
Y
Iwama
Atsushi
A
Nakauchi
Hiromitsu
H
Masui
Shinji
S
Niwa
Hitoshi
H
Nishimoto
Masazumi
M
Muramatsu
Masami
M
Okuda
Akihiko
A
D000818:Animals; D001921:Brain / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental; D024002:HMGB Proteins; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics*; D011247:Pregnancy; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors; D014162:Transfection; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism
D004268:DNA-Binding Proteins; D024002:HMGB Proteins; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D009687:Nuclear Proteins; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D014157:Transcription Factors