BioProject

The epigenetic changes of the chromatin represent an attractive molecular substrate for adaptation to the environment. More...

The epigenetic changes of the chromatin represent an attractive molecular substrate for adaptation to the environment. We examined here the role of CBP, a histone acetyltransferase involved in mental retardation, in the genesis and maintenance of long-lasting systemic and behavioral adaptations to environmental enrichment (EE). Morphological and behavioral analyses demonstrated that EE ameliorates deficits associated to CBP-deficiency. However, CBP-deficient mice also showed a strong defect in environment-induced neurogenesis and impaired EE-enhanced spatial navigation and patter separation ability. These defects correlated with an attenuation of the transcriptional program induced in response to EE and with deficits in histone acetylation at the promoters of EE-regulated, neurogenesis-related genes. Additional experiments in CBP restricted and inducible knockout mice indicated that environment-induced adult neurogenesis is extrinsically regulated by CBP function in mature granule cells. Overall, our experiments demonstrate that the environment alters gene expression by impinging on activities involved in modifying the epigenome and identify CBP-dependent transcriptional neuroadaptation as an important mediator of EE-induced benefits, a finding with important implications for mental retardation therapeutics. To identify those genes whose expression was altered in the hippocampus of cbp heterozygous mice both under basal conditions and after 2 weeks of exposure to environmental enrichment, we performed a gene profiling analysis of hippocampal tissue using high-density oligonucleotide microarrays. Overall design: We obtained quintuplicate (standard housing) and triplicate (environmental enrichment) samples containing total RNA from the hippocampi of four 3-month old females of either genotype (in total 32 cbp+/- mice and 32 wild type littermates were used in the experiment). Less...