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Chunk #27 — Molecular basis for the effect of maternal care on HPA responses to stress

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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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that the relative activity of the individual exon 1 sequences is similar, with one notable exception, the exon 17 promoter sequence. The fused exon 17 has the highest transcriptional activity of any single promoter construct. More recent studies confirm the transactivational effect of NGFIA at the exon 17sequence. We used a cotransfection model with human embryonic kidney (HEK) cells (intentionally aiming as far from the neural target as possible) with an NGFIA expression vector and an exon 17-luciferase construct. Cotransfection of the NGFIA vector and the exon 17-luciferase construct resulted in a robust increase in luciferase activity, reflecting NGFIA-induced activation of transcription through the exon 17 promoter. These later studies reveal not only the ability of the exon 17 promoter to drive gene expressions, but that it does so in response to an increased NGFIA signal. Recall that an NGFIA antisense completely blocks the effects of 5-HT on GR expression in hippocampal cell cultures.80