title: SUV39H1 orchestrates temporal dynamics of centromeric methylation essential for faithful chromosome segregation in mitosis.
abstract: Histone methylation performs multiple functions such as DNA replication, transcription regulation, heterochromatin formation, and chromatin condensation. How this methylation gradient is orchestrated in the centromere during chromosome segregation is not known. Here we examine the temporal dynamics of protein methylation in the centromere by SUV39H1 methyltransferase, a key mitotic regulator, using fluorescence resonance energy transfer-based sensors in living HeLa cells and immunofluorescence of native SUV39H1 substrates. A quantitative analysis of methylation dynamics, using centromere-targeted sensors, reveals a temporal change during chromosome segregation. These dynamics result in an accurate chromosome congression to and alignment at the equator as an inhibition of methylation dynamics using SUV39H1 inhibitor perturbs chromosome congression in living HeLa cells. Surprisingly, this inhibition of methylation results in a brief increase in Aurora B kinase activity and an enrichment of microtubule depolymerase MCAK in the centromere with a concomitant kinetochore-microtubule destabilization and a reduced tension across the sister kinetochores with ultimate chromosome misalignments. We reason that SUV39H1 generates a gradient of methylation marks at the kinetochore that provides spatiotemporal information essential for accurate chromosome segregation in mitosis.
authors: Anhui Key Laboratory for Cellular Dynamics and Chemical Biology, University of Science & Technology of China School of Life Sciences, Anhui 230026, China.
authors: Lingluo
authors: L
authors: Chu
authors: Tongge
authors: T
authors: Zhu
authors: Xing
authors: X
authors: Liu
authors: Ruoying
authors: R
authors: Yu
authors: Methode
authors: M
authors: Bacanamwo
authors: Zhen
authors: Z
authors: Dou
authors: Youjun
authors: Y
authors: Chu
authors: Hanfa
authors: H
authors: Zou
authors: Gary H
authors: GH
authors: Gibbons
authors: Dongmei
authors: D
authors: Wang
authors: Xia
authors: X
authors: Ding
authors: Xuebiao
authors: X
authors: Yao
mesh_terms: D064107:Aurora Kinase B; D064127:Aurora Kinases; D002503:Centromere / Q000378:metabolism*; D020090:Chromosome Segregation / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D012097:Repressor Proteins; C407843:SUV39H1 protein, human; D008780:Methyltransferases; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases