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Jonathan D. Turner

Dept. Immunology,
Laboratoire Nationale de Santé / CRP-Santé
20A rue Auguste Lumiere
Grand Duchy of Luxembourg
As the leader of the PsychoImmunology group, my interest is in explaining the transcriptional regulation of the glucocorticoid receptor. Aberrant GR levels are associated with stress-related disorders such as depression, and affect social behaviour, mood, learning and memory. Dissecting how tissue-specific GR levels are regulated, in particular in the brain, is the first step towards understanding the mechanisms underlying aberrant GR levels in disease and altered behaviour.

Over the last few years we have shown that the unique variability in the 5’ region of the GR gene, with 9 alternative first exons and 13 splice variants plays a critical role in transcriptional control maintaining homeostasis of the gluco-corticoid receptor (GR). This 5’mRNA heterogeneity, common to all species investigated, remains untrans-lated since the alternative first exons are spliced to exon 2 immediately upstream of the translation initia-tion codon. These alternative first exons are located either immediately upstream of the coding exons in the CpG island (exons B-H and J), or further upstream (exons 1A and 1I). The mechanisms regulating the differential usage of these first exons in different tissues and individuals, and the role of the 5’UTR in the splicing of the coding exons are still poorly understood. Data from our laboratory and others have shown that the multiple first exons represent only a first layer of complexity orchestrated probably by tissue-specific transcription factors. Modulation of alternative first exon activity by epigenetic methylation of their promoters represents a second layer of complexity at least partially controlled by perinatal programming. The alternative promoter usage also appears to affect the 3’ splicing generating the different GR coding variants, GRalpha, GRbeta, and GR-P.

It is anticipated that the group will continue working on understanding the transcriptional control of the GR, including investigating the role of microRNA, and detailed epigenetic studies to determine their effects on GR transcription.
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