REGULATION OF THE OCT-4 GENE BY NUCLEAR RECEPTORS

To unravel the network of transcription factors established during dev elopment it is important to understand how genes specifically expresse d during embryogenesis are regulated. Oct-4 is a transcription factor whose expression is associated with an undifferentiated cell phenotype in the early mouse embryo and is downregulated when such cells differ entiate. An enhancer in the upstream region of Oct-4 has previously be en reported as being sufficient to mediate the cell-type specific expr ession and RA-dependent down-regulation in EC cells, although the enha ncer contains no retinoic acid receptor (RAR) binding sites. Here we r eport the identification of promoter elements important for the regula tion of the Oct-4 gene in EC cells. A region of the proximal Oct-4 pro moter contains an overlapping set of regulatory elements including a h igh affinity binding site for Sp1 and three direct repeats of an AGGTC A-like sequence with either +1 or 0 spacing. Binding and transient tra nsfection assays reveal that Oct-4 is subject to negative regulation b y different members of the steroid-thyroid hormone receptor superfamil y. Specifically, important roles for ARP-1 and RAR in Oct-4 expression are indicated.