Structural Variants of Binding Sites for Glucocorticoid Receptor and the Mechanisms of Glucocorticoid Regulation: Analysis of Gr-trrd Database

Motivation: Glucocorticoid receptor (GR) is an important regulator of many genes involved in a variety of biochemical and physiological processes. The features of the structure and localization of DNA binding sites for GR may be significant for ensuring specificity of glucocorticoid-mediated regulation of different genes. Results: GR-TRRD database accumulates the largest out of currently published samples of nucleotide sequences that are experimentally proved to bind GR (glucocorticiod receptor binding sites, GRbss). This sample consists of 152 GRbss from 77 genes controlled by glucocorticoids. Analysis of the sample has shown that the structure of only half of GRbss (53 %) corresponds to traditional viewpoint about structural organization of glucocorticoid response element (GRE) as an inverted repeat of hexameric half-site sequence TGTTCT (Aranda, Pascual, 2001). 40 % of GRbss contain only hexameric half-site. Notably, there exist experimental evidence about participation of most of these GRbss in glucocorticoid regulation. As a result of increasing the number of sequences in the sample of GRbss, we have specified the consensus of sites organized in a form of inverted repeat (palindromic GREs). Also, possible mechanisms of action of hexameric half-sites in glucocorticoid induction have been discussed. Availability: (http://wwwmgs.bionet.nsc.ru/mgs/papers /merkulova/gluc/).