Identification of both general and region-specific embryonic CNS enhancer elements in the nestin promoter.
In this report, we investigate how nestin expression is controlled in neural progenitor cells of the embryonic CNS. A 374-bp region in the second intron of the human nestin gene is sufficient, and a 120-bp sequence in this region is required, to express the lacZ reporter gene throughout the developing CNS of E9.5-10.5 transgenic mouse embryos. The 120-bp element region contains putative binding sites for nuclear hormone receptors and we show that TRs, RXR, RAR, and COUP-TF bind to these motifs. A separate enhancer, located most probably 5' to the 120-bp sequence in the second intron, controls midbrain expression at E10.5. In conclusion, our data show that the nestin enhancer in the second intron contains elements both for general and for region-specific CNS progenitor cell expression and suggest that nuclear hormone receptors play a role in the regulation of nestin expression in the early CNS.
Lothian
C
C
Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institute, Stockholm, S-171 77, Sweden.
Prakash
N
N
Lendahl
U
U
Wahlström
G M
GM
D000818:Animals; D001483:Base Sequence; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology*; D004742:Enhancer Elements, Genetic; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008636:Mesencephalon / Q000196:embryology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D064231:Nestin; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D047488:Retinoid X Receptors; D013234:Stem Cells; D014157:Transcription Factors / Q000378:metabolism*
D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D047488:Retinoid X Receptors; D014157:Transcription Factors