RESUMEN
The in vivo three-dimensional genomic architecture of adult mature neurons at homeostasis and after medically relevant perturbations such as axonal injury remains elusive. Here, we address this knowledge gap by mapping the three-dimensional chromatin architecture and gene expression program at homeostasis and after sciatic nerve injury in wild-type and cohesin-deficient mouse sensory dorsal root ganglia neurons via combinatorial Hi-C, promoter-capture Hi-C, CUT&Tag for H3K27ac and RNA-seq. We find that genes involved in axonal regeneration form long-range, complex chromatin loops, and that cohesin is required for the full induction of the regenerative transcriptional program. Importantly, loss of cohesin results in disruption of chromatin architecture and severely impaired nerve regeneration. Complex enhancer-promoter loops are also enriched in the human fetal cortical plate, where the axonal growth potential is highest, and are lost in mature adult neurons. Together, these data provide an original three-dimensional chromatin map of adult sensory neurons in vivo and demonstrate a role for cohesin-dependent long-range promoter interactions in nerve regeneration.
Asunto(s)
Axones , Cromatina , Cohesinas , Regeneración Nerviosa , Regiones Promotoras Genéticas , Células Receptoras Sensoriales , Animales , Células Receptoras Sensoriales/metabolismo , Células Receptoras Sensoriales/fisiología , Ratones , Regiones Promotoras Genéticas/genética , Cromatina/metabolismo , Regeneración Nerviosa/genética , Regeneración Nerviosa/fisiología , Axones/metabolismo , Axones/fisiología , Humanos , Proteínas Cromosómicas no Histona/metabolismo , Proteínas Cromosómicas no Histona/genética , Elementos de Facilitación Genéticos/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Ganglios Espinales/metabolismo , Ganglios Espinales/citología , Nervio Ciático/metabolismoRESUMEN
The in vivo three-dimensional genomic architecture of adult mature neurons at homeostasis and after medically relevant perturbations such as axonal injury remains elusive. Here we address this knowledge gap by mapping the three-dimensional chromatin architecture and gene expression programme at homeostasis and after sciatic nerve injury in wild-type and cohesin-deficient mouse sensory dorsal root ganglia neurons via combinatorial Hi-C and RNA-seq. We find that cohesin is required for the full induction of the regenerative transcriptional program, by organising 3D genomic domains required for the activation of regenerative genes. Importantly, loss of cohesin results in disruption of chromatin architecture at regenerative genes and severely impaired nerve regeneration. Together, these data provide an original three-dimensional chromatin map of adult sensory neurons in vivo and demonstrate a role for cohesin-dependent chromatin interactions in neuronal regeneration.
RESUMEN
Photosynthetic biomaterials have attracted considerable attention at different levels of the biological organisation, from molecules to the biosphere, due to a variety of artificial application possibilities. During photosynthesis, the first steps of the conversion of light energy into chemical energy take place in a pigment-protein complex, called reaction centre (RC). In our experiments photosynthetic reaction centre protein, purified from Rhodobacter sphaeroides R-26 purple bacteria, was bound to porous silicon pillars (PSiP) after the electropolymerisation of aniline onto the surface. This new type of biohybrid material showed remarkable photoactivity in terms of measured photocurrent under light excitation in an electrochemical cell. The photocurrent was found to increase considerably after the addition of ubiquinone (UQ-0), an e--acceptor mediator of the RC. The photoactivity of the complex was found to decrease by the addition of terbutryn, the chemical which inhibits the e--transport on the acceptor side of the RC. In addition to the generation of sizeable light-induced photocurrents, using the PSiP/RC photoactive hybrid nanocomposite material, the system was found to be sensitive towards RC inhibitors and herbicides. This highly ordered patterned 3D structure opens new solution for designing low-power (bio-)optoelectronic, biophotonic and biosensing devices.