Mega-Enhancer Bodies Organize Neuronal Long Genes in the Cerebellum.

Dynamic regulation of gene expression plays a key role in establishing the diverse neuronal cell types in the brain. Recent findings in genome biology suggest that three-dimensional (3D) genome organization has important, but mechanistically poorly understood functions in gene transcription. Beyond local genomic interactions between promoters and enhancers, we find that cerebellar granule neurons undergoing differentiation in vivo exhibit striking increases in long-distance genomic interactions between transcriptionally active genomic loci, which are separated by tens of megabases within a chromosome or located on different chromosomes. Among these interactions, we identify a nuclear subcompartment enriched for near-megabase long enhancers and their associated neuronal long genes encoding synaptic or signaling proteins. Neuronal long genes are differentially recruited to this enhancer-dense subcompartment to help shape the transcriptional identities of granule neuron subtypes in the cerebellum. SPRITE analyses of higher-order genomic interactions, together with IGM-based 3D genome modeling and imaging approaches, reveal that the enhancer-dense subcompartment forms prominent nuclear structures, which we term mega-enhancer bodies. These novel nuclear bodies reside in the nuclear periphery, away from other transcriptionally active structures, including nuclear speckles located in the nuclear interior. Together, our findings define additional layers of higher-order 3D genome organization closely linked to neuronal maturation and identity in the brain.

Appetitive information seeking behaviour reveals robust daily rhythmicity for Internet-based food-related keyword searches.

There has been an exponential growth of information seeking behaviour (ISB) via Internet-based programs over the past decade. The availability of software that record ISB temporal patterns has provided a valuable opportunity to examine biological rhythms in human behaviour. Internet search repositories, such as Google Trends, permit the analyses of large datasets that can be used to track ISB on a domestic and international scale. We examined daily and seasonal Google Trends search patterns for keywords related to food intake, using the most relevant search terms for the USA, UK, Canada, India and Australia. Daily and seasonal ISB rhythmicity were analysed using CircWave v. 1.4. Daily ISB data revealed a robust and significant sine waveform for general terms (e.g. 'pizza delivery') and country-specific search terms (e.g. 'just eat'). The pattern revealed clear evening double-peaks, occurring every day at 19.00 and 02.00. The patterns were consistent across search terms, days of the week and geographical locations, suggesting a common ISB rhythm that is not necessarily culture-dependent. Then, we conducted Cosinor v. 2.4 analyses to examine the daily amplitudes in ISB. The results indicated a non-significant linear increased from Monday to Sunday. Seasonal data did not show consistent significant ISB patterns. It is likely that two different human populations are responsible for the daily 'early' and 'late' evening ISB peaks. We propose that the major factor that contributes to the bimodal evening peak is age-dependent (e.g. adolescent, early adulthood versus midlife and mature adulthood) and a minor role for human chronotypes (e.g. late versus early). Overall, we present novel human appetitive behaviour for information seeking of food resources and propose that Internet-based search patterns reflect a biological rhythm of motivation for energy balance.