In:
Nature Communications, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2021-12-13)
Abstract:
Regulatory mechanisms associated with repeat-rich sequences and chromosomal conformations in mature neurons remain unexplored. Here, we map 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 B 2 NeuN+ megabase-scaling subcompartment. Single molecule long-read sequencing and comparative Hi-C chromosomal contact mapping in wild-derived SPRET/EiJ ( Mus spretus ) and laboratory inbred C57BL/6J ( Mus musculus ) reveal neuronal reconfigurations tracking recent ERV2 expansions in the murine germline, with significantly higher B 2 NeuN+ contact frequencies at sites with ongoing insertions in Mus musculus . Neuronal ablation of the retrotransposon silencer Kmt1e/Setdb1 triggers B 2 NeuN+ disintegration and rewiring with open chromatin domains enriched for cellular stress response genes, along with severe neuroinflammation and proviral assembly with infiltration of dendrites . We conclude that neuronal megabase-scale chromosomal architectures include an evolutionarily adaptive heterochromatic organization which, upon perturbation, results in transcriptional dysregulation and unleashes ERV2 proviruses with strong neuronal tropism.
Type of Medium:
Online Resource
ISSN:
2041-1723
DOI:
10.1038/s41467-021-26862-z
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2021
detail.hit.zdb_id:
2553671-0
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