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| Status |
Public on Oct 11, 2021 |
| Title |
NEURON-SPECIFIC CHROMOSOMAL MEGADOMAIN ORGANIZATION IS ADAPTIVE TO RECENT RETROTRANSPOSON EXPANSIONS |
| Organisms |
Mus musculus; Mus spretus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Other
|
| Summary |
Here, we mapped cell-type specific chromatin domain organization in adult mouse cerebral cortex and report strong enrichment of Endogenous Retrovirus 2 (ERV2) repeat sequences in the neuron-specific heterochromatic 'B2NeuN+' megabase-scaling subcompartment. Comparative chromosomal conformation mapping in Mus spretus and Mus musculus revealed neuron-specific reconfigurations tracking recent ERV2 retrotransposon expansions in the murine germline, with significantly higher B2 megadomain contact frequencies at sites with ongoing ERV2 insertions in Mus musculus. Ablation of the retrotransposon silencer Kmt1e/Setdb1 (KO) triggered B2 megadomain disintegration and rewiring with open chromatin domains enriched for cellular stress response genes, along with severe neuroinflammation and proviral assembly of ERV2/Intracisternal-A-Particles (IAPs) infiltrating dendrites and spines. We conclude that neuronal megadomain architectures include evolutionarily adaptive heterochromatic organization which, upon perturbation, unleashes ERV proviruses with strong tropism within mature neurons.
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| Overall design |
Chromatin configurations, histone modifications, RNA, and open chromatin profiles in wildtype and Setdb1 fl/fl x Camk2a-Cre mice; chromatin configurations in SPRET/EiJ and C57/BL6J mice; targeted de novo insertions in wildtype mice
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| Contributor(s) |
Chandrasekaran S, Espeso-Gil S, Loh YE, Javidfar B, Kassim B, Dong Y, Zhu Y, Bicks LK, Rajarajan P, Peter CJ, Agullo-Pascual E, Iskhakova M, Estill M, Shen L, Jiang Y, Akbarian S |
| Citation(s) |
34903713 |
| |
| Submission date |
Mar 09, 2021 |
| Last update date |
Jan 10, 2022 |
| Contact name |
Sandhya Chandrasekaran |
| E-mail(s) |
sandhya.chandrasekaran@icahn.mssm.edu
|
| Phone |
5104568992
|
| Organization name |
Icahn School of Medicine at Mount Sinai
|
| Department |
Psychiatry
|
| Lab |
Akbarian
|
| Street address |
1470 Madison Avenue, 9-202, Hess Building
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10029 |
| Country |
USA |
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| Platforms (5)
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| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL21273 |
HiSeq X Ten (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (72)
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| Relations |
| BioProject |
PRJNA708211 |
| SRA |
SRP309932 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE168524_09_18_18_glia_pooled_neurons_males_allValidPairs.hic |
6.0 Gb |
(ftp)(http) |
HIC |
| GSE168524_09_21_18_A002A005_male_neurons_pooled_allValidPairs.hic |
4.4 Gb |
(ftp)(http) |
HIC |
| GSE168524_RAW.tar |
23.8 Gb |
(http)(custom) |
TAR (of HIC, TXT) |
| GSE168524_counttab.repeat.rna.kowt.ALL.txt.gz |
99.8 Mb |
(ftp)(http) |
TXT |
| GSE168524_female_glia_allValidPairs.hic |
7.1 Gb |
(ftp)(http) |
HIC |
| GSE168524_h3k27ac-diffReps.txt.gz |
11.7 Mb |
(ftp)(http) |
TXT |
| GSE168524_h3k79me2-diffReps.txt.gz |
606 b |
(ftp)(http) |
TXT |
| GSE168524_h3k9me3-diffReps.txt.gz |
2.9 Mb |
(ftp)(http) |
TXT |
| GSE168524_insituHi-C-FEM-Pool1-A015A19_pooled_allValidPairs.hic |
5.4 Gb |
(ftp)(http) |
HIC |
| GSE168524_insituWTKO-A01519_stedb1_pooled_males_neurons_allValidPairs.hic |
4.6 Gb |
(ftp)(http) |
HIC |
| GSE168524_neurons_fem_wt_allValidPairs.hic |
5.2 Gb |
(ftp)(http) |
HIC |
| GSE168524_rna-total-counts.xls.gz |
5.5 Mb |
(ftp)(http) |
XLS |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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