STRUCTURE AND PROMOTER ANALYSIS OF THE GENE ENCODING THE MOUSE HELIX-LOOP-HELIX FACTOR HES-5 - IDENTIFICATION OF THE NEURAL PRECURSOR CELL-SPECIFIC PROMOTER ELEMENT
K. Takebayashi et al., STRUCTURE AND PROMOTER ANALYSIS OF THE GENE ENCODING THE MOUSE HELIX-LOOP-HELIX FACTOR HES-5 - IDENTIFICATION OF THE NEURAL PRECURSOR CELL-SPECIFIC PROMOTER ELEMENT, The Journal of biological chemistry, 270(3), 1995, pp. 1342-1349
HES-5 is a mammalian basic helix-loop-helix factor that has a distant
sequence homology to the product of the Drosophila pair-rule gene hair
y. HES-5 mRNA is present exclusively in the developing nervous system,
but its level decreases as neural differentiation proceeds. In this s
tudy, to characterize the molecular mechanism of the neural-specific e
xpression of HES-5 we isolated the mouse HES-5 gene. This gene consist
s of three exons, and Southern blot analysis shows that it is a single
copy gene. The transcription initiation site, determined by primer ex
tension and reverse transcriptase-mediated polymerase chain reaction,
is located 26 nucleotides downstream of a TATA box. Transient transfec
tion analysis shows that the upstream region of the HES-5 gene can dir
ect efficient expression in neural precursor cells and moderate expres
sion in undifferentiated NCB20 neuroblastoma-brain hybrid cells but no
t in glioma or fibroblast cells. The moderate level of expression in N
CB20 cells decreases when differentiation into neuron-like cells is in
duced. Further promoter analysis shows that this undifferentiated neur
al-specific expression is mediated by the multiple GC stretches presen
t in the HES-5 promoter. Gel mobility shift analysis suggests the pres
ence of a neural precursor cell-specific protein that binds to the GC
stretches. These results raise the possibility that HES-5 expression i
n the developing nervous system is regulated by the GC stretch-binding
protein.