Nde1 is required for heterochromatin compaction and stability in neocortical neurons
Alison A. Chomiak, Yan Guo, Caroline A. Kopsidas, Dennis P. McDaniel, Clara C. Lowe, Hongna Pan, Xiaoming Zhou, Qiong Zhou, Martin L. Doughty, Yuanyi Feng
Abstract
aberrations remains elusive. Here we demonstrate Nde1 controls neurogenesis through facilitating H4K20 trimethylation-mediated heterochromatin compaction. This mechanism patterns diverse chromatin landscapes and stabilizes constitutive heterochromatin of neocortical neurons. We demonstrate that NDE1 can undergo dynamic liquid-liquid phase separation, partitioning to the nucleus and interacting with pericentromeric and centromeric satellite repeats. Nde1 LOF results in nuclear architecture aberrations and DNA double-strand breaks, as well as instability and derepression of pericentromeric satellite repeats in neocortical neurons. These findings uncover a pivotal role of NDE1/Nde1 in establishing and protecting neuronal heterochromatin. They suggest that heterochromatin instability predisposes a wide range of brain dysfunction.