No man is an island, and no neuron is either: complex, intricate connections between and among brain cells are needed for the brain to do its job correctly. Now, researchers from Japan have uncovered a fundamental mechanism that lets neurons know when and how to form these connections.<\/p>\n\n\n\n
In the study \u00abRepetitive CREB-DNA interactions at gene loci predetermined by CBP induce activity-dependent gene expression in human cortical neurons,\u00bb recently published<\/a> in Cell Reports<\/em>, researchers from Osaka University and Shenzhen Bay Laboratory have revealed the behavior of proteins linked to learning and memory in human brain cells<\/a>.<\/p>\n\n\n\n In the developing brain, neuronal activity<\/a> stimulates the expression of genes that are needed for brain cells to grow and form connections. If this process is disrupted, developmental and psychiatric disorders can develop.<\/p>\n\n\n\n \u00abThe transcription factor cAMP response element binding protein (CREB) is required for the brain to learn and form memories,\u00bb says lead author of the study Yuri Atsumi. \u00abWhile CREB and CREB binding protein (CBP) are known to interact to stimulate gene expression in the developing brain, it is unclear how neuronal activity affects this interaction.\u00bb<\/p>\n\n\n\n To explore this, the researchers used a sophisticated microscopy technique called single-molecule imaging to track the movements of CREB and CBP in human brain cells.<\/p>\n\n\n\n \u00abThe results were very clear,\u00bb explains co-senior author Noriyuki Sugo. \u00abWe found that neuronal activity markedly increased repetitive, long-term interactions between CREB and DNA and between CREB and CBP.\u00bb<\/p>\n\n\n\n These interactions attracted RNA polymerase II, which activates gene expression. Furthermore, the researchers discovered that the sites where CREB interacted with DNA to promote gene expression<\/a> require prior acetylation mediated by CBP.<\/p>\n\n\n\n \u00abThese findings not only elucidate the mechanism underlying learning and memory in developing brain<\/a>, but also offer new insight into how psychiatric disorders may develop,\u00bb says co-senior author Nobuhiko Yamamoto.<\/p>\n\n\n\n Given that CBP is a gene that can cause Rubinstein\u2013Taybi syndrome, in which patients show mental retardation<\/a> and intellectual disability<\/a>, inactivation of the CBP protein could help explain how this disease develops. Exploring CREB-CBP interactions further in 3D brain-like models could yield additional insight into the effects of neuronal activity observed in this study.<\/p>\n\n\n\n More information:<\/strong> Yuri Atsumi et al, Repetitive CREB-DNA interactions at gene loci predetermined by CBP induce activity-dependent gene expression in human cortical neurons, Cell Reports<\/em> (2023). DOI: 10.1016\/j.celrep.2023.113576<\/a><\/p>\n\n\n\n Journal information:<\/strong> Cell Reports<\/a> <\/a><\/p>\n\n\n\n Provided by\u00a0Osaka University<\/a>\u00a0<\/p>\n\n\n\n