靶向从头形成的果蝇着丝粒揭示了 CENP-A 染色质的可塑性和维持潜力。
Targeted De Novo Centromere Formation in Drosophila Reveals Plasticity and Maintenance Potential of CENP-A Chromatin.
机构信息
Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269, USA.
Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269, USA; Institute for Systems Genomics, University of Connecticut, Storrs, CT 06269, USA.
出版信息
Dev Cell. 2020 Feb 10;52(3):379-394.e7. doi: 10.1016/j.devcel.2020.01.005.
Centromeres are essential for accurate chromosome segregation and are marked by centromere protein A (CENP-A) nucleosomes. Mis-targeted CENP-A chromatin has been shown to seed centromeres at non-centromeric DNA. However, the requirements for such de novo centromere formation and transmission in vivo remain unknown. Here, we employ Drosophila melanogaster and the LacI/lacO system to investigate the ability of targeted de novo centromeres to assemble and be inherited through development. De novo centromeres form efficiently at six distinct genomic locations, which include actively transcribed chromatin and heterochromatin, and cause widespread chromosomal instability. During tethering, de novo centromeres sometimes prevail, causing the loss of the endogenous centromere via DNA breaks and HP1-dependent epigenetic inactivation. Transient induction of de novo centromeres and chromosome healing in early embryogenesis show that, once established, these centromeres can be maintained through development. Our results underpin the ability of CENP-A chromatin to establish and sustain mitotic centromere function in Drosophila.
着丝粒对于染色体的准确分离至关重要，由着丝粒蛋白 A（CENP-A）核小体标记。已经表明，靶向错误的 CENP-A 染色质会在非着丝粒 DNA 处引发着丝粒。然而，这种新形成的着丝粒在体内的形成和传递的要求仍然未知。在这里，我们使用果蝇和 LacI/lacO 系统来研究靶向新形成的着丝粒在发育过程中的组装和遗传能力。新形成的着丝粒能够在六个不同的基因组位置有效地形成，这些位置包括活跃转录的染色质和异染色质，并导致广泛的染色体不稳定。在连接过程中，新形成的着丝粒有时会占上风，导致通过 DNA 断裂和 HP1 依赖性表观遗传失活而失去内源性着丝粒。新形成的着丝粒在早期胚胎发生中的瞬时诱导和染色体修复表明，一旦建立，这些着丝粒可以在发育过程中维持。我们的结果为 CENP-A 染色质在果蝇中建立和维持有丝分裂着丝粒功能提供了支持。
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