Molecular Genetics of Human Cognition

Nuclear function in cognitive disorder. Consolidation of long-term memory requires the regulation of gene expression. Active Rsk2 phosphorylates the transcription factor, CREB. P-CREB recruits the coactivator CREB binding protein (CBP) and promotes transcription of genes whose promoters contain CRE sites. MeCP2 permanently represses expression of some genes that are methylated in CpG islands found in the promoters. Loss of MeCP2 causes an aberrant increase in the dosage of some genes, usually genes that undergo imprinting. Expansion of trinucleotide repeat sequences in genes changes local chromatin structure and influences RNA metabolism, leading to the dysregulation of several genes. Presence of an extra chromsome (trisomy) results in pathological over-expression of potentially hundreds of genes.