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Biology subjects

Rehn, M.

Publications and source records attributed to Rehn, M..

2 recordsLinked to original sources

Shapes of synaptic protein distributions distinguish brain architectures

Neuronal activity is the result of the orchestrated actions of multitudes of synapses, acting and evolving not as individuals, but as populations. We therefore collected, for millions of synapses, a functionally relevant proxy for their strengths. Namely, we measured postsynaptic protein content by deploying a fluorescent PSD95 variant. Then we summarized, by statistical moments, the shapes of the distributions of protein contents, over local synaptic populations. In this way we explored the hypothesis that such collective properties inform on brain architectures. Our measurements cover complete parasagittal sections of the mouse brain, in animals one week to 18 months old. We identified a hierarchical organization of regions along the anterior-posterior axis, with three main clusters of divergent synaptic population shapes. One includes telencephalic regions, one is centered in the midbrain and hindbrain, and one comprises mainly the thalamus and the cerebellum. The structure emerging from our approach aligns with discoveries in studies of regional patterns of cellular gene expressions. Our results suggest that synaptic populations are dynamically regulated over the lifespan. Regions which at three months of age have thinner tails largely conserve their distribution shapes later in life, whereas heavy tails in other regions strikingly grow ever more so.

neuroscience↗

LncRNA Dio3os regulates neighboring gene Dio3 and impacts osteogenesis in trans

Long non-coding RNAs (lncRNAs) frequently act at imprinted loci, yet how a single lncRNA can simultaneously activate its neighbor and repress distant genes through a shared chromatin platform remains poorly defined. We show that imprinted Dio3os performs this bifunctional role by scaffolding the nucleosome remodeling and histone deacetylase (NuRD-HDAC1) complex. ATAC-seq and ChIP-seq across osteoblast differentiation reveal that the Dio3-Dio3os bidirectional promoter is dynamically remodeled and co-occupied by HDAC1, HIF1, and active histone marks. CRISPR-mediated exon deletion, CRISPRi, and polyadenylation termination demonstrate that Dio3os activates Dio3 in cis while repressing osteogenic genes in trans. RIP-MS and reverse pulldown identify direct Dio3os-NuRD interaction; ChIP shows the same machinery produces opposing H3K27ac outcomes at Dio3os versus osteogenic promoters. In vivo, osteoblast-specific CRISPRi increases trabecular and cortical bone mass, whereas CRISPRa reduces it in both sexes. Dio3os couples chromatin remodeling to thyroid-hormone metabolism through a context-dependent NuRD scaffold. One sentence summaryDio3os scaffolds NuRD-HDAC1 to activate Dio3 in cis and repress thyroid-hormone-responsive osteogenic genes in trans.

molecular biology↗