T. Eisen et al., THE POU DOMAIN TRANSCRIPTION FACTOR BRN-2 - ELEVATED EXPRESSION IN MALIGNANT-MELANOMA AND REGULATION OF MELANOCYTE-SPECIFIC GENE-EXPRESSION, Oncogene, 11(10), 1995, pp. 2157-2164
Previous work has shown that melanoma cell lines express a distinct oc
tamer binding protein. Given the role of octamer-binding proteins in c
ell differentiation and development, the role this factor is a key iss
ue in understanding melanocyte differentiation and transformation. Usi
ng a proteolytic clipping assay, we show that the melanoma-specific oc
tamer factor is Brn-2/N-Oct3, a POU domain protein previously known to
be expressed in adult brain and in the developing nervous system. N-O
ct3 mRNA was detected in a range of human melanoma cell lines and was
around 10-fold elevated compared to normal human melanocytes while mRN
A for Brn-2 was also detected in a mouse melanoblast cell line. Expres
sion of Brn-2/N-Oct3, in melanoma cells in cotransfection assays activ
ated the expression of the MHC class II DR alpha promoter but represse
d the activity of the melanocyte-specific tyrosinase promoter. Repress
ion correlated with Brn-2/N-Oct3 binding in a mutually exclusive fashi
on with basic-helix-loop-helix-leucine-zipper (bHLH-LZ) transcription
factor USF in vitro and with Brn-2 expression preventing activation of
the tyrosinase promoter by the bHLH-LZ factor Microphthalmia in vivo.
The potential role of Brn-2/N-Oct3 in melanocyte differentiation and
gene expression is discussed.