The glucocorticoid receptor gene exon 1-F promoter is not methylated at the NGFI-A binding site in human hippocampus.
Recent research has demonstrated that early life experience, such as variation in maternal care, can have a profound impact on the physiological and endocrine stress response of Rattus norvegicus. Low maternal care resulted in increased methylation of the nerve growth factor-inducible protein A (NGFI-A, EGR1) binding site located in the hippocampal glucocorticoid receptor gene (Nr3c1) exon 1(7) promoter, leading to decreased Nr3c1 expression, which results in a reduced efficiency of glucocorticoid-mediated negative feedback on hypothalamus-pituitary-adrenal axis activity. The human glucocorticoid receptor gene (NR3C1) has a highly similar 5' structure compared to the rat, and the human alternative exon 1-F is the orthologue to the rat exon 1(7). Based upon the evidence from rats, and the high sequence identity of the regulatory sequences, we examined the methylation pattern of the corresponding NGFI-A binding site in the human glucocorticoid receptor exon 1-F specific promoter in post mortem hippocampal tissue. In contrast to the findings in rats, neither of the two CpG motifs within the NGFI-A binding site was methylated in the 32 subjects investigated. These observations might reflect different promoter methylation patterns in humans and rats.
Moser
Dirk
D
Department of Neuro-Behavioral Genetics, University of Trier, Trier, Germany. moser@uni-trier.de
Molitor
Anne
A
Kumsta
Robert
R
Tatschner
Thomas
T
Riederer
Peter
P
Meyer
Jobst
J
D001344:Autopsy; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D019175:DNA Methylation; D005091:Exons; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*
C094815:NAB1 protein, human; C497713:NR3C1 protein, human; D011965:Receptors, Glucocorticoid; D012097:Repressor Proteins; D004247:DNA