Transcriptional control of human Glucocorticoid Receptor (GR)

[Transkriptionskontrolle des Glucocorticoidrezeptors (GR) beim Menschen]
The complicated human alternative GR promoter region plays a pivotal role in the regulation of GR levels. In this thesis, both genomic and environmental factors linked with GR expression are covered. This research showed that GR promoters were susceptible to silencing by methylation and the activity of the individual promoters was also modulated by SNPs. E2F1 is a major element to drive the expression of GR 1F transcripts and single CpG dinucleotide methylation cannot mediate the inhibition of transcription in vitro. Also, the distribution of GR first exons and 3" splice variants (GRα and GR-P) is expressed throughout the human brain with no region-specific alternative first exon usage. These data mirrored the consistently low levels of methylation in the brain, and the observed homogeneity throughout the studied regions. Taken together, the research presented in this thesis explored several layers of complexity in GR transcriptional regulation.