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Chunk #54 — 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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the NGFIA expression vector significantly increases luciferase activity; however, this effect is dramatically reduced if the CpG dinucleotides within the exon 17 sequence are methylated. Moreover, the effect of NGFIA on transcription through an exon 17-luciferase reporter construct was almost completely abolished with a point mutation at the 5' cytosine (a cytosine to adenosine mutation). Taken together, these findings suggest that an “epimutation” at a single cytosine within the NGFIA consensus sequence alters the binding of NGFIA and might therefore explain the sustained effect of maternal care on hippocampal GR expression and HPA responses to stress.