S. Carreira et al., The gene encoding the T-box factor Tbx2 is a target for the microphthalmia-associated transcription factor in melanocytes, J BIOL CHEM, 275(29), 2000, pp. 21920-21927
Commitment to the melanocyte lineage is characterized by the onset of micro
phthalmia-associated transcription factor (Mitf) expression. Mitf plays a f
undamental role in melanocyte development, with mice lacking Mitf being ent
irely devoid of pigment cells. In the absence of functional Mitf protein, m
elanoblasts expressing Mitf mRNA disappear around 2 days after their first
appearance either by apoptosis or by losing their identity and adopting an
alternative cell fate. The role of Mitf must therefore be to regulate genes
required for melanoblast survival, proliferation, or the maintenance of me
lanoblast identity. Yet to date, Mitf has been shown to regulate genes such
as Tyrosinase, Tyrp-1, and Dct, which are required for pigmentation, a dif
ferentiation-specific process. Because expression of these genes cannot acc
ount for the complete absence of pigment cells in Mitf-negative mice, Mitf
must regulate the expression of other as yet uncharacterized genes. Here we
provide several lines of evidence to suggest that Mitf may regulate the ex
pression of the Tbx2 transcription factor, a member of the T-box family of
proteins implicated in the maintenance of cell identity. First, isolation a
nd sequencing of the entire murine Tbx2 gene revealed that the Tbx2 promote
r contains a full consensus Mitf recognition element; second, Mitf could bi
nd the promoter in vitro and activate Tbx2 expression in vivo in an E box-d
ependent fashion; and third, Tbx2 is expressed in melanoma cell lines expre
ssing Mitf, but not in a line in which Mitf expression was not detectable.
Taken together, with the fact that Tbx2 is expressed in Mitf-positive melan
oblasts and melanocytes, but not in Mitf-negative melanoblast precursor cel
ls, the evidence suggests that the Tbx2 gene may represent one of the first
known targets for Mitf that is not a gene involved directly in the manufac
ture of pigment.