Functional characterization of a natural retinoic acid responsive element

M. M.V. Ruiz d., T. H. Bugge, P. Hirschmann, H. G. Stunnenberg

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92 Citaten (Scopus)

Samenvatting

Retinoic acid receptor (RAR) and thyroid hormone receptor (T3R) are thought to bind as dimers to a T3 responsive element (T3REpal) comprised of inverted repeats of the half-site motif GGTCA. However, a RA responsive element (βRARE) was previously identified in the promoter of the RARβ2 gene which contains two direct repeats of the motif GTTCA spaced by a six nucleotide gap. We now demonstrate the ability of RARα, β and γ to bind to and transactivate through this element and that the two direct repeats comprise the βRARE. Surprisingly, the GTTCA motifs rearranged to form a palindrome do not confer RA responsiveness to a heterologous promoter. Furthermore, no significant level of transactivation is detected by ligand-activated RAR through the Moloney murine leukaemia virus T3RE, which comprises two direct repeats of the sequence GGTCA/C spaced by a five nucleotide gap. Similarly, T3R does not induce gene expression through the βRARE. This study establishes the preference of T3R to transactivate through direct repeats spaced by a five nucleotide gap as opposed to a six nucleotide gap. In contrast, RAR appears to be more flexible with respect to spacing requirements between repeats, although higher levels of transactivation are obtained through direct repeats spaced by a six nucleotide gap. Interestingly, although some elements mediate either RA or T3 induction, changing a single nucleotide in the MoMLV T3RE with a five nucleotide spacing creates a promiscuous RA/T3 responsive element.

Originele taal-2Engels
Pagina's (van-tot)3829-3838
Aantal pagina's10
TijdschriftEMBO Journal
Volume10
Nummer van het tijdschrift12
DOI's
StatusGepubliceerd - 1991
Extern gepubliceerdJa

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