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LRIF1 interacts with HP1α to coordinate accurate chromosome segregation during mitosis Free
Saima Akram 1,† , Fengrui Yang 1,2,† , Junying Li 1,† , Gregory Adams 2,3 , Yingying Liu 1,2 ,Xiaoxuan Zhuang 1,3 , Lingluo Chu 4 , Xu Liu 1,2 , Nerimah Emmett 2 , Winston Thompson 2 ,McKay Mullen 2 , Saravana Muthusamy 2 , Wenwen Wang 1,2 , Fei Mo 1,3,* , and Xing Liu 1,2,*
1 Anhui Key Laboratory for Cellular Dynamics, University of Science & Technology of China School of Life Sciences, National Science Center for Physical Sciences at Nanoscale, and Chinese Academy of Science Center of Excellence on Molecular Cell Sciences, Hefei 230027, China
2 Keck Center for Molecular Imaging, Department of Physiology, Morehouse School of Medicine, Atlanta, GA 30310, USA
3 National Institutes of Health, Bethesda, MD 20892, USA
4 Department of Molecular Cell Biology, Harvard University, Cambridge, MA 02138, USA
These authors contributed equally to this work.
*Correspondence to:* Correspondence to: Fei Mo, E-mail: fei.mo@nih.gov; Xing Liu, E-mail: xing1017@ustc.edu.cn
J Mol Cell Biol, Volume 10, Issue 6, December 2018, Pages 527-538  https://doi.org/10.1093/jmcb/mjy040
Keyword: HP1α, LRIF1, mitosis, centromere, chromosome segregation

Heterochromatin protein 1α (HP1α) regulates chromatin specification and plasticity during cell fate decision. Different structural determinants account for HP1α localization and function during cell division cycle. Our earlier study showed that centromeric localization of HP1α 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 HP1α to the centromere of mitotic chromosomes and its interaction with HP1α is essential for accurate chromosome segregation during mitosis. LRIF1 interacts directly with HP1α chromoshadow domain via an evolutionarily conserved PXVXL motif within its C-terminus. Importantly, the LRIF1–HP1α interaction is critical for Aurora B activity in the inner centromere. Mutation of PXVXL motif of LRIF1 leads to defects in HP1α centromere targeting and aberrant chromosome segregation. These findings reveal a previously unrecognized direct link between LRIF1 and HP1α in centromere plasticity control and illustrate the critical role of LRIF1–HP1α interaction in orchestrating accurate cell division.