Topic: H3K27ac

With age, differentiated cells undergo a progressive erosion of epigenetic landscape and loss of cellular identity. Specifically, epigenetic aging involves H3K27ac depletion at cellular identity genes and their subsequent repression, together with H3K27me3-mediated derepression of developmental genes, normally silenced in differentiated cells. Yet, it is unclear whether such a mechanism occurs in brain cells, particularly in neurons, and whether it might contribute to neurodegenerative process, such that at play in Huntington’s disease (HD), a striatal neurodegenerative disease. In previous st

Huntington's disease (HD) is a genetic neurodegenerative disease that damages primarily the striatum and leads to motor, cognitive and psychiatric symptoms. The HD striatum undergoes early specific epigenetic gene reprogramming, leading to progressive impairment of striatal neuron identity and function. Notably, genes that define striatal neuron identity are progressively down-regulated due to decreased histone acetylation (e.g. H3K27 acetylation -H3K27ac-). Additionally, developmental genes show an increase in H3K27ac, leading to their derepression. Histone acetylation is strongly connected t

Activity-driven transcription is a crucial step in neuronal plasticity processes. We found that during neuronal activation induced by the proepileptic drug kainic acid, there is a dramatic genomic redistribution of the transcriptional cofactors CBP and p300. These cofactors leave their default location at enhancer and promoter regions related with cell identity to occupy regulatory regions at activity-induced genes. In parallel with these changes, we also detect changes in the levels of H3K27ac and chromatin accessibility accordingly with the redistribution and modification of the epigenetic c