S. Plaza et al., C-MYB ACTS AS TRANSCRIPTIONAL ACTIVATOR OF THE QUAIL PAX6 (PAX-QNR) PROMOTER THROUGH 2 DIFFERENT MECHANISMS, Oncogene, 10(2), 1995, pp. 329-340
To understand the regulation of the Pax-6 gene, which plays an importa
nt role in eye development, we have characterized the promoter region
of the quail Pax-6(Pax-QNR) gene. In addition to TATA and CAAT boxes,
sequence analysis revealed several putative cis-regulatory elements am
ong which three myb-responsive elements (MRE). C-myb encodes a nuclear
, DNA-binding phosphoprotein that functions as transcriptional regulat
or. Co-transfection in quail embryo cells of the Pax-QNRlpax-6 promote
r with a vector expressing the 75 kDa c-myb protein resulted in an inc
rease in Pax-QNR promoter activity. By footprinting experiments we ide
ntified multiple binding sites for the myb protein within the promoter
region. Protein containing the myb DNA-binding domain fused to the VP
16-transactivation domain was fully efficient in Pax-QNR promoter tran
sactivation, demonstrating that myb can transactivate through a direct
binding on DNA. However, a myb truncated protein devoid of DNA-bindin
g domain was also able to transactivate the Pax-QNR promoter. These re
sults show that this promoter can be transactivated by the myb protein
directly as well as indirectly. Finally we show by in situ hybridizat
ion that c-myb is strongly expressed in the developing neuroretina, si
multaneously with Pax-QNR. These observations suggest that the c-myb p
rotein may be a regulator of Pax-QNR/pax-6.