DNA-Binding Elements of Nuclear Receptors, HREs

The steroid hormone receptors are sequence specific DNA binding proteins whose cognate DNA elements are termed hormone responsive elements (HREs). The HREs known to date possess a common structure. They are composed primarily of two copies of a hexamer sequence. In table 4.1 are listed the hexamer sequences of the HREs of important nuclear receptors. 

The receptors bind to the cognate HRE mainly as dimers, allowing the formation of homodimers as well as heterodimers between various receptor monomers. We know of very few nuclear receptors whose HRE contains only a single copy of the recognition sequence. These receptors bind as monomers to the cognate HRE. 

Based on the subunit structure of DNA bound receptors and on the structure of the HREs, four classes of nuclear receptors can be distinguished (fig. 4.7). 

The HREs of the steroid hormone receptors posses a palindromic structure, comparable to the DNA binding elements of procaryotic repressors (see fig. 4.7a). The glucocorticoid receptor, for example, binds as a homodimer to the two-fold symmetrical recognition sequence, whereby the receptor is already dimerized in solution. In complex with the DNA each subimit of the dimer contacts one half-site of the HRE. As a consequence of the two-fold repeat of the recognition sequence, a high affinity binding of the receptor dimer results (compare 1.2.4). 

The DNA binding element of the nuclear receptors for all-trans retinoic acid, for 9-cis retinoic acid, for the T3 hormone and for the vitamin D3 hormone usually exhibit a direct repeat of the recognition sequence, resulting in formation of heterodimers on the DNA (fig. 4.7b). One of the partners in the heterodimer is always the receptor for 9-cis retinoic acid, RXR, and which usually occupies the 5 side of the HRE. 

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