Centromere identity is defined by nucleosomes containing CENP-A,a histone H3 variant.The deposition of CENP-A at centromeres is tightly regulated in a cell-cycle-dependent manner.We previously reported that the spatio...Centromere identity is defined by nucleosomes containing CENP-A,a histone H3 variant.The deposition of CENP-A at centromeres is tightly regulated in a cell-cycle-dependent manner.We previously reported that the spatiotemporal control of centromeric CENP-A incorporation is mediated by the phosphorylation of CENP-A Ser68.However,a recent report argued that Ser68 phosphoregulation is dispensable for accurate CENP-A loading.Here,we report that the substitution of Ser68 of endogenous CENP-A with either Gln68 or Glu68 severely impairs CENP-A deposition and cell viability.We also find that mice harboring the corresponding mutations are lethal.Together,these results indicate that the dynamic phosphorylation of Ser68 ensures cell-cycle-dependent CENP-A deposition and cell viability.展开更多
The genetic information,stored in the linear sequences of DNA,encodes all of the genes that a living organism uses to produce proteins and RNAs essential for various cellular functions.In eukaryotes,however,genomic DN...The genetic information,stored in the linear sequences of DNA,encodes all of the genes that a living organism uses to produce proteins and RNAs essential for various cellular functions.In eukaryotes,however,genomic DNA is hierarchically and efficiently packaged into multiple-level chromatin structures within the nucleus,including the nucleosome,30 nm fibers,chromatin loops,topology associated domains(TADs).展开更多
基金This work was supported by the Ministry of Science and Technology of China(2017YFA0504202 and 2019YFA0508903)the National Natural Science Foundation of China(31991161 and 32070604)+1 种基金the Beijing Municipal Science and Technology Committee(Z201100005320013)HHMI International Research Scholar grant(55008737).
文摘Centromere identity is defined by nucleosomes containing CENP-A,a histone H3 variant.The deposition of CENP-A at centromeres is tightly regulated in a cell-cycle-dependent manner.We previously reported that the spatiotemporal control of centromeric CENP-A incorporation is mediated by the phosphorylation of CENP-A Ser68.However,a recent report argued that Ser68 phosphoregulation is dispensable for accurate CENP-A loading.Here,we report that the substitution of Ser68 of endogenous CENP-A with either Gln68 or Glu68 severely impairs CENP-A deposition and cell viability.We also find that mice harboring the corresponding mutations are lethal.Together,these results indicate that the dynamic phosphorylation of Ser68 ensures cell-cycle-dependent CENP-A deposition and cell viability.
文摘The genetic information,stored in the linear sequences of DNA,encodes all of the genes that a living organism uses to produce proteins and RNAs essential for various cellular functions.In eukaryotes,however,genomic DNA is hierarchically and efficiently packaged into multiple-level chromatin structures within the nucleus,including the nucleosome,30 nm fibers,chromatin loops,topology associated domains(TADs).
