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.Ou...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 receptorinteracting factor 1 (LRIF1),which recruits HPla to the centromere of mitotic chromosomes and its interaction with HP1α is essential for accurate chromosome segregation during mitosis.LRIF1 interacts directly with HPla chromoshadow domain via an evolutionariLy conserved PXVXL motif within its C-terminus.Importantly,the LRIF1-HPla interaction is critical for Aurora B activity in the inner centromere.Mutation of PXVXL motif of LRIF1 Leads to defects in HPla 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.展开更多
基金grants from the Ministry of Science and Technology of the People's Republic of China (2017YFA0503600 and 2016YFA0100500)the National Natural Science Foundation of China (31430054,31320103904, 91313303,31621002,31501095,and 31671405)+1 种基金the Ministry of Education of the People's Republic of China (IRT_17R102)the US National Institutes of Health (CA164133,DK56292, and DKl15812).
文摘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 receptorinteracting factor 1 (LRIF1),which recruits HPla to the centromere of mitotic chromosomes and its interaction with HP1α is essential for accurate chromosome segregation during mitosis.LRIF1 interacts directly with HPla chromoshadow domain via an evolutionariLy conserved PXVXL motif within its C-terminus.Importantly,the LRIF1-HPla interaction is critical for Aurora B activity in the inner centromere.Mutation of PXVXL motif of LRIF1 Leads to defects in HPla 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.
