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| Status |
Public on Jan 18, 2024 |
| Title |
Histone methylation mediated by NSD1 is required for the establishment and maintenance of neuronal identities [WGBS] |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
The formation of the mammalian neocortex during development requires coordinated establishment of functional regions at proper anterior-posterior and medial-lateral positions – area patterning, as well as neocortical layers. Although key transcription factors (TFs) were known to specify and maintain cell fates, mechanisms underlying how TFs are precise expressed and repressed are largely elusive. Here we showed that NSD1, the methyltransferase for histone H3 lysine 36 dimethylation (H3K36me2), controls both areal and layer identities of the neocortex. Nsd1-ablated neocortex showed prominent areal shift of all four primary functional regions and aberrant wiring of major cortico-thalamic-cortical projections. Nsd1 conditional knockout mice displayed defects in spatial memory, motor learning and coordination, reminiscent of patients with the Sotos syndrome carrying NSD1 mutations. Although projection neurons (PN) of neocortical layers were mostly properly produced and positioned upon Nsd1 deletion, post-mitotic PNs could not establish their layer-specific identities. More strikingly, in adult Nsd1 conditional knockout neocortices, superficial-layer PNs progressively mis-expressed markers for deep-layer PNs. Moreover, neocortical PNs ablated with Nsd1 remained immature morphologically and electrophysiologically. Loss of NSD1 in post-mitotic 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. Our findings revealed that H3K36me2 mediated by NSD1 is required for establishment and maintenance of region- and layer-specific neocortical identities.
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| Overall design |
Whole-genome bisulfite sequencing in somatosensory cortices of 2.5 month old mice.
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| Contributor(s) |
Zheng Y, Zhao C, Song Q, Xu L, Zhang B, Kong X, Li S, Li X, Shen Y, Zhuang L, Wu M, Liu Y, Zhou Y |
| Citation(s) |
37995181 |
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| Submission date |
Apr 10, 2023 |
| Last update date |
Jan 18, 2024 |
| Contact name |
zhao chen |
| E-mail(s) |
2018202040127@whu.edu.cn
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| Phone |
17647413608
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| Organization name |
wuhan university
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| Department |
BIOLOGY
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| Lab |
Yan Zhou lab
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| Street address |
shuiguohu
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| City |
wuhan |
| State/province |
Hubei |
| ZIP/Postal code |
430072 |
| Country |
China |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE229341 |
Histone methylation mediated by NSD1 is required for the establishment and maintenance of neuronal identities |
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| Relations |
| BioProject |
PRJNA954034 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE229340_WGBS_cKO_vs_Ctrl_DMR_all_result.txt.gz |
4.5 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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