The Sox2 regulatory region 2 functions as a neural stem cell-specific enhancer in the telencephalon

Satoru Miyagi, Masazumi Nishimoto, Tetsuichiro Saito, Mikiko Ninomiya, Kazunobu Sawamoto, Hideyuki Okano, Masami Muramatsu, Hideyuki Oguro, Atsushi Iwama, Akihiko Okuda

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Abstract

Sox2 is expressed at high levels in neuroepithelial stem cells and persists in neural stem/progenitor cells throughout adulthood. We showed previously that the Sox2 regulatory region 2 (SRR2) drives strong expression in these cells. Here we generated transgenic mouse strains with the β-geo reporter gene under the control of the SRR2 in order to examine the spatiotemporal function of this regulatory region. We show that the SRR2 functions specifically in neural stem/progenitor cells. However, unlike Nestin 2nd intronic enhancer, the SRR2 shows strong regional specificity functioning only in restricted areas of the telencephalon but not in any other portions of the central nervous system such as the spinal cord. We also show by in vitro clonogenic assay that at least some of these SRR2-functioning cells possess the hallmark properties of neural stem cells. In adult brains, we could detect strong β-geo expression in the subventricular zone of the lateral ventricle and along the rostral migrating stream where actively dividing cells reside. Chromatin immunoprecipitation assays reveal interactions of POU and Sox factors with SRR2 in neural stem/progenitor cells. Our data also suggest that the specific recruitment of these proteins to the SRR2 in the telencephalon defines the spatiotemporal activity of the enhancer in the developing nervous system.

Original languageEnglish
Pages (from-to)13374-13381
Number of pages8
JournalJournal of Biological Chemistry
Volume281
Issue number19
DOIs
Publication statusPublished - 2006 May 12

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Miyagi, S., Nishimoto, M., Saito, T., Ninomiya, M., Sawamoto, K., Okano, H., Muramatsu, M., Oguro, H., Iwama, A., & Okuda, A. (2006). The Sox2 regulatory region 2 functions as a neural stem cell-specific enhancer in the telencephalon. Journal of Biological Chemistry, 281(19), 13374-13381. https://doi.org/10.1074/jbc.M512669200