NEURON-SPECIFIC CHROMOSOMAL MEGADOMAIN ORGANIZATION IS ADAPTIVE TO RECENT RETROTRANSPOSON EXPANSIONS
NEURON-SPECIFIC CHROMOSOMAL MEGADOMAIN ORGANIZATION IS ADAPTIVE TO RECENT RETROTRANSPOSON EXPANSIONS
ABSTRACT 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 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.
Javidfar Behnam、Dong Yuhao、Rajarajan Prashanth、Estill Molly、Shen Li、Loh Yong-Hwee Eddie、Chandrasekaran Sandhya、Kassim Bibi、Iskhakova Marina、Zhu Yueyan、Akbarian Schahram、Agullo-Pascual Esperanza、Bicks Lucy K.、Espeso-Gil Sergio、Peter Cyril J.、Jiang Yan
Icahn School of Medicine at Mount SinaiInstitutes of Brain Science at Fudan UniversityIcahn School of Medicine at Mount SinaiIcahn School of Medicine at Mount SinaiIcahn School of Medicine at Mount SinaiIcahn School of Medicine at Mount SinaiIcahn School of Medicine at Mount SinaiIcahn School of Medicine at Mount SinaiIcahn School of Medicine at Mount SinaiInstitutes of Brain Science at Fudan UniversityIcahn School of Medicine at Mount SinaiIcahn School of Medicine at Mount SinaiIcahn School of Medicine at Mount SinaiIcahn School of Medicine at Mount SinaiIcahn School of Medicine at Mount SinaiInstitutes of Brain Science at Fudan University
遗传学细胞生物学分子生物学
Javidfar Behnam,Dong Yuhao,Rajarajan Prashanth,Estill Molly,Shen Li,Loh Yong-Hwee Eddie,Chandrasekaran Sandhya,Kassim Bibi,Iskhakova Marina,Zhu Yueyan,Akbarian Schahram,Agullo-Pascual Esperanza,Bicks Lucy K.,Espeso-Gil Sergio,Peter Cyril J.,Jiang Yan.NEURON-SPECIFIC CHROMOSOMAL MEGADOMAIN ORGANIZATION IS ADAPTIVE TO RECENT RETROTRANSPOSON EXPANSIONS[EB/OL].(2025-03-28)[2025-05-15].https://www.biorxiv.org/content/10.1101/2021.08.30.458289.点此复制
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