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Chunk #51 — Site-specific methylation of the 5' CpG dinucleotide of the NGFIA response element blocks transcription factor binding

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Environmental programming of stress responses through DNA methylation: life at the interface between a dynamic environment and a fixed genome.
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This is an important finding for our understanding of the processes by which maternal care programs hippocampal GR expression and thus HPA responses to stress. While there are substantial differences in differences in NGFIA expression between the offspring of high- and low-LG mothers in early postnatal life, no such differences are apparent in adulthood. Our hypothesis is that the cytosine methylation in the response element for NGFIA interferes with NGFIA binding to the GR exon 17 promoter. We therefore predicted that the reduced cytosine methylation in the adult offspring of high-LG compared with low-LG mothers would result in greater NGFIA binding to the exon 17 promoter. This prediction was confirmed using a ChIP assay (described above) examining in vivo formation of protein-DNA complexes in hippocampal tissue from adult animals.67 The results indicated a threefold greater binding of NGFIA protein to the hippocampal exon 17 GR promoter in the adult offspring of high-LG compared with low-LG mothers. Using the same tissue samples and an antibody against the acetylated form of H3, we67 found dramatically increased acetylated H3 association with the exon