Abstract
Glucocorticoid receptor binds half sites as a monomer and regulates specific target genes
Highlights
Glucocorticoid receptor (GR) is a hormone-activated, Deoxyribonucleic acid (DNA)-binding transcriptional regulatory factor that controls inflammation, metabolism, stress responses, and other physiological processes
Different GR alleles induce diverse, gene-specific transcriptional responses To improve our understanding of the patterns of GR functional surfaces used during transcriptional regulation, we carried out a genome-wide analysis in a series of human U2OS osteosarcoma cell lines with stably integrated GR alleles [2,6]
Each GRα mutation alters in a distinct way the utilization of various GR regulatory surfaces; among cells expressing the 30iiB, A477T, or E773R mutations, a panel of 10 regulated genes displayed six out of the eight possible patterns of surface utilization of three surfaces compared to GRα; that is, (2 states, utilizes or does not)(3 mutations) = 8 patterns [2]
Summary
Glucocorticoid receptor (GR) is a hormone-activated, DNA-binding transcriptional regulatory factor that controls inflammation, metabolism, stress responses, and other physiological processes. GR employs different patterns of functional surfaces of GR to regulate different target genes. Glucocorticoid receptor (GR, HUGO symbol NR3C1) is a DNA-binding transcriptional regulatory factor that is activated by binding glucocorticoid hormones, and which regulates diverse aspects of physiology. In vitro, purified GR recognizes a GR binding sequence (GBS) motif composed of imperfect palindromic 6 base pair (bp) ‘half sites’ separated by 3 bp ‘spacers’, binding as an inverted dimer [5]. It is reassuring that GBS motifs drive GR-regulated transcription in a simple reporter context [5], and reasonable to assume that GR occupancy at GBRs that contain GBSs reflects in vivo sequence recognition. Rules dictating the relationship between DNA sequence, GR conformation, and utilization of distinct GR functional surfaces remain unknown
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