| Experiment Id | GSE181331 | Name | Post-mitotic H3.3 deposition in new neurons mediates acquisition of neuronal transcriptome and identity |
| Experiment Type | RNA-Seq | Study Type | WT vs. Mutant |
| Source | GEO | Curation Date | 2023-03-08 |
| description | Histone variants are deposited DNA synthesis-independently and provide replacement histones in terminally postmitotic cells, including neurons. Histone variants also serve active roles in nucleosomal and gene regulatory functions. Here, we find that newborn cortical neurons substantially incorporate H3.3 post-mitosis. Co-deletion of H3.3 genes H3f3a and H3f3b from new neurons abrogates this incorporation, and disrupts the developmental acquisition of neuronal transcriptome, identity, and axon projections. Stage-dependent deletion of H3.3 genes from: 1) cycling neural progenitor cells, 2) neurons immediately after terminal mitosis, or 3) several days later, revealed the first postmitotic days as a critical window for de novo H3.3. This early H3.3 deposition differs in timescale from H3.3 turnover, which we find to occur over weeks in cortical neurons. Thus, our study uncovers an active role for H3.3 in establishing neuronal transcriptome and identity immediately post-mitosis that is distinct from its role in maintaining H3 levels over the neuronal lifespan. We analyzed a total of 12 samples of rRNA-depleted RNA from P0 mouse cortex using UMI RNA-seq. Libraries were generated using Click-seq. 4 samples were controls, 4 samples were H3.3 Neurod6-Cre conditional knockouts and 4 samples were H3.3 Emx1-Cre conditional knockouts. |
