| First Author | Zheng Y | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 12 | Pages | 113496 |
| PubMed ID | 37995181 | Mgi Jnum | J:344238 |
| Mgi Id | MGI:7574066 | Doi | 10.1016/j.celrep.2023.113496 |
| Citation | Zheng Y, et al. (2023) Histone methylation mediated by NSD1 is required for the establishment and maintenance of neuronal identities. Cell Rep 42(12):113496 |
| abstractText | Appropriate histone modifications emerge as essential cell fate regulators of neuronal identities across neocortical areas and layers. Here we showed that NSD1, the methyltransferase for di-methylated lysine 36 of histone H3 (H3K36me2), controls both area and layer identities of the neocortex. Nsd1-ablated neocortex showed an area shift of all four primary functional regions and aberrant wiring of cortico-thalamic-cortical projections. Nsd1 conditional knockout mice displayed defects in spatial memory, motor learning, and coordination, resembling patients with the Sotos syndrome carrying NSD1 mutations. On Nsd1 loss, superficial-layer pyramidal neurons (PNs) progressively mis-expressed markers for deep-layer PNs, and PNs remained immature both morphologically and electrophysiologically. Loss of Nsd1 in postmitotic PNs causes genome-wide loss of H3K36me2 and re-distribution of DNA methylation, which accounts for diminished expression of neocortical layer specifiers but ectopic expression of non-neural genes. Together, H3K36me2 mediated by NSD1 is required for the establishment and maintenance of region- and layer-specific neocortical identities. |
