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| Status |
Public on Sep 25, 2023 |
| Title |
KDM2B regulates hippocampal morphogenesis by transcriptionally silencing Wnt signaling in neural progenitors (ATAC-Seq) |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The hippocampus plays major roles in learning and memory. Similar to other parts of the brain, the development of hippocampus requires precise coordination of patterning, cell proliferation, differentiation, and migration, with both cell-intrinsic and extrinsic mechanisms involved. Here we genetically removed the chromatin-association capability of KDM2B - a key component of the variant Polycomb repressive complex 1 (PRC1) - in the developing dorsal telencephalon (Kdm2bEmx1-∆CxxC) to surprisingly discover that the size of Kdm2bEmx1-∆CxxC hippocampus, particularly the dentate gyrus, became drastically smaller with disorganized cellular components and structure. Kdm2bEmx1-∆CxxC mice displayed prominent defects in spatial memory, motor learning and fear conditioning. The differentiation path of the developing Kdm2bEmx1-∆CxxC hippocampus was greatly delayed, with significant amount of TBR2-expressing intermediate progenitors being stuck along the migratory path. Transcriptome and chromatin immunoprecipitation studies of neonatal hippocampi and their progenitors indicated that genes implicated in stemness maintenance, especially components of canonical Wnt signaling, could not be properly silenced by PRC1 and PRC2. Activating Wnt signaling disturbed hippocampal neurogenesis, recapitulating the effect of KDM2B loss. Together, we unveiled a previously unappreciated gene repressive program mediated by KDM2B that controls progressive fate specifications and cell migration, hence morphogenesis of hippocampus during development.
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| Overall design |
Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for histone H2AK119ub1, H3K27me3 as well as the histone modifications H3K36me2 in P0 hippocampus and neurosphere. Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) for P0 hippocampus.
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| Contributor(s) |
Zhang B, Zhao C, Shen W, Li W, Zheng Y, Kong X, Wang J, Wu X, Liu Y, Zhou Y |
| Citation(s) |
37838801 |
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| Submission date |
Jan 09, 2023 |
| Last update date |
Oct 31, 2023 |
| 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: |
| GSE222465 |
KDM2B regulates hippocampal morphogenesis by transcriptionally silencing Wnt signaling in neural progenitors |
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| Relations |
| BioProject |
PRJNA922153 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE222462_RAW.tar |
2.7 Mb |
(http)(custom) |
TAR (of NARROWPEAK) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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