LRIF1 interacts with HP1α to coordinate accurate chromosome segregation during mitosis
LRIF1 interacts with HP1α to coordinate accurate chromosome segregation during mitosis
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LRIF1 与 HP1α 相互作用，协调有丝分裂过程中准确的染色体分离
DOI：
10.1093/jmcb/mjy040
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发表时间：
2018-12-01
影响因子：
5.5
通讯作者：
Liu, Xing
中科院分区：
文献类型：
--
作者：
Akram, Saima;Yang, Fengrui;Liu, Xing
异染色质蛋白1 α（HP 1 α）在细胞命运决定过程中调节染色质特化和可塑性。不同的结构决定因子解释了HP 1a在细胞分裂周期中的定位和功能。我们早期的研究表明，HP 1 α的着丝粒定位依赖于间期的表观遗传标记H3 K9 me 3，而其在有丝分裂中的着丝粒定位依赖于未表征的PXVXL-含有因子。在这里，我们确定了一个含有PXVXL的蛋白质，配体依赖性核受体相互作用因子1（LRIF 1），它招募HP 1a的有丝分裂染色体的着丝粒和它的相互作用与HP 1 α是必不可少的准确的染色体分离在有丝分裂。LRIF 1通过其C-末端内进化上保守的PXVXL基序直接与HP 1 α chromoshadow结构域相互作用。重要的是，LRIF 1-HP 1 α相互作用对于内着丝粒中的极光B活性至关重要。LRIF 1的PXVXL基序突变导致HP 1 α着丝粒靶向缺陷和异常染色体分离。这些发现揭示了LRIF 1和HP 1a在着丝粒可塑性控制中以前未被认识到的直接联系，并说明了LRIF 1-HP 1 α相互作用在协调准确的细胞分裂中的关键作用。
Heterochromatin protein 1 alpha (HP1 alpha) regulates chromatin specification and plasticity during cell fate decision. Different structural determinants account for HP1a localization and function during cell division cycle. Our earlier study showed that centromeric localization of HP1 alpha depends on the epigenetic mark H3K9me3 in interphase, while its centromeric location in mitosis relies on uncharacterized PXVXL-containing factors. Here, we identified a PXVXL-containing protein, ligand-dependent nuclear receptor-interacting factor 1 (LRIF1), which recruits HP1a to the centromere of mitotic chromosomes and its interaction with HP1 alpha is essential for accurate chromosome segregation during mitosis. LRIF1 interacts directly with HP1 alpha chromoshadow domain via an evolutionarily conserved PXVXL motif within its C-terminus. Importantly, the LRIF1-HP1 alpha interaction is critical for Aurora B activity in the inner centromere. Mutation of PXVXL motif of LRIF1 leads to defects in HP1 alpha centromere targeting and aberrant chromosome segregation. These findings reveal a previously unrecognized direct link between LRIF1 and HP1a in centromere plasticity control and illustrate the critical role of LRIF1-HP1 alpha interaction in orchestrating accurate cell division.