Department of Life Sciences, Imperial College London, London, United Kingdom.
Lehrstuhl für Genetik, University of Bayreuth, Bayreuth, Germany.
Elife. 2020 Apr 7;9:e55159. doi: 10.7554/eLife.55159.
Condensin complexes are essential for mitotic chromosome assembly and segregation during cell divisions, however, little is known about their functions in post-mitotic cells. Here we report a role for the condensin I subunit Cap-G in neurons. We show that, despite not requiring condensin for mitotic chromosome compaction, post-mitotic neurons express Cap-G. Knockdown of Cap-G specifically in neurons (from their birth onwards) results in developmental arrest, behavioural defects, and dramatic gene expression changes, including reduced expression of a subset of neuronal genes and aberrant expression of genes that are not normally expressed in the developing brain. Knockdown of Cap-G in mature neurons results in similar phenotypes but to a lesser degree. Furthermore, we see dynamic binding of Cap-G at distinct loci in progenitor cells and differentiated neurons. Therefore, Cap-G is essential for proper gene expression in neurons and plays an important role during the early stages of neuronal development.
凝缩复合物对于有丝分裂染色体的组装和细胞分裂过程中的分离至关重要，但对于它们在后有丝分裂细胞中的功能知之甚少。在这里，我们报告了一个关于凝缩复合物 I 亚基 Cap-G 在神经元中的作用。我们发现，尽管在后有丝分裂的神经元中不需要凝缩复合物来进行有丝分裂染色体的压缩，但它们仍然表达 Cap-G。特异性地在神经元中（从其出生开始）敲低 Cap-G 会导致发育停滞、行为缺陷和显著的基因表达变化，包括一组神经元基因的表达降低和通常不在发育中的大脑中表达的基因的异常表达。在成熟神经元中敲低 Cap-G 会导致类似的表型，但程度较轻。此外，我们还观察到 Cap-G 在祖细胞和分化神经元中的不同位置的动态结合。因此，Cap-G 对于神经元中的正确基因表达是必不可少的，并且在神经元发育的早期阶段发挥着重要作用。
