Researchers from Osaka University and Shenzhen Bay Laboratory in Japan have made a significant discovery involving the mechanisms behind gene expression in brain development. The team focused on the behavior of proteins linked to learning and memory in human brain cells and uncovered a fundamental mechanism that regulates the formation of connections between neurons.
The study, published in Cell Reports, sheds light on the role of the transcription factor cAMP response element binding protein (CREB) and its interaction with the CREB binding protein (CBP) in stimulating gene expression. The researchers aimed to understand how neuronal activity affects this interaction and how disruptions in the process can lead to developmental and psychiatric disorders.
Lead author Yuri Atsumi emphasized the importance of CREB in learning and memory in the brain. However, the precise impact of neuronal activity on the interaction between CREB and CBP remained unknown. To address this gap in knowledge, the researchers utilized a technique called single-molecule imaging, a sophisticated microscopy method that allowed them to track the movements of CREB and CBP in human brain cells.
The results of the study were illuminating. The researchers observed that neuronal activity significantly increased the frequency and duration of interactions between CREB and DNA, as well as between CREB and CBP. These interactions were found to attract RNA polymerase II, an enzyme that activates gene expression. Additionally, the findings highlighted the role of CBP-mediated acetylation in facilitating the interaction between CREB and DNA for gene expression.
Co-senior author Noriyuki Sugo noted the clarity of the results, highlighting the long-term and repetitive nature of the interactions. The study not only provides insights into the mechanisms underlying learning and memory in brain development, but also offers new perspectives on the development of psychiatric disorders.
Co-senior author Nobuhiko Yamamoto emphasized the potential implications of the study’s findings for Rubinstein-Taybi syndrome. CBP, the gene associated with this condition, plays a crucial role in the process of gene expression. Understanding the inactivation of CBP protein could help explain the mental retardation and intellectual disability observed in patients with Rubinstein-Taybi syndrome.
Moving forward, the researchers suggest that exploring CREB-CBP interactions in 3D brain-like models could yield further insights into the effects of neuronal activity. Such models could provide a more comprehensive understanding of brain development and the factors influencing gene expression.
This breakthrough research paves the way for future studies aimed at unraveling the complexities of brain development and shedding light on the mechanisms underlying various neurological disorders. Understanding these processes at a molecular level could ultimately open new avenues for therapeutic interventions and strategies for addressing developmental and psychiatric disorders.