Nucleic Acids Research, 1994, Vol. 22, No. 6 901-911
© 1994
MOLECULAR BIOLOGY |
Regulation of the Oct-4 gene by nuclear receptors
EMBL, Gene Expression Programme Meyerhofstrasse 1, 69012 Heidelberg, Germany
* To whom correspondence should be addressed
Received January 24, 1994. Revised February 22, 1994. Accepted February 22, 1994.
To unravel the network of transcription factors established during development it is important to understand how genes specifically expressed 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 differentiate. An enhancer in the upstream region of Oct-4 has previously been reported as being sufficient to mediate the cell-type specific expression and RA-dependent down-regulation in EC cells, although the enhancer contains no retinoic acid receptor (RAR) binding sites. Here we report the Identification of promoter elements important for the regulation of the Oct-4 gene In EC cells. A region of the proximal Oct-4 promoter contains an overlapping set of regulatory elements Including a high affinity binding site for Sp1 and three direct repeats of an AGGTCA-like sequence with either +1 or 0 spacing. Binding and transient transfectlon assays reveal that Oct-4 is subject to negative regulation by different members of the steroidthyroid hormone receptor superfamily. Specifically, important roles for ARP-1 and RAR in Oct-4 expression are indicated.
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