Eukaryotic genomic DNA is highly packaged into chromatin by histones to fit inside the nucleus. Other than the bulk packaging role of canonical histones with an expression peak at S phase and replication-coupled depos...Eukaryotic genomic DNA is highly packaged into chromatin by histones to fit inside the nucleus. Other than the bulk packaging role of canonical histones with an expression peak at S phase and replication-coupled deposition, different histone variants have evolved distinct regulatory mechanisms for their expression, deposition and functional implications. The diversity of histone variants results in structural plasticity of chromatin and highlights functionally distinct chromosomal domain, which plays critical roles in development from a fertilized egg into a complex organism, as well as in aging and diseases. However, the mechanisms of this fundamental process are poorly understood so far. It is of particular interest to investigate how the variants are incorporated into chromatin and mark specific chromatin states to regulate gene expression, and how they are involved in development and diseases. In this review, we focus on recent progress in studies of epigenetic regulation of three extensively investigated variants including H2A.Z, macroH2A and H3.3, and their functional implications in development and diseases.展开更多
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
基金supported by the grants from the Ministry of Science and Technology(Nos.2011CB966300 to G.L.and 2009CB825501 to P.C.)the National Natural Science Foundation of China(Nos.91019007,31071147,91219202 to G.L.,and 31000566 to P.C.)the Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry to P.C
文摘Eukaryotic genomic DNA is highly packaged into chromatin by histones to fit inside the nucleus. Other than the bulk packaging role of canonical histones with an expression peak at S phase and replication-coupled deposition, different histone variants have evolved distinct regulatory mechanisms for their expression, deposition and functional implications. The diversity of histone variants results in structural plasticity of chromatin and highlights functionally distinct chromosomal domain, which plays critical roles in development from a fertilized egg into a complex organism, as well as in aging and diseases. However, the mechanisms of this fundamental process are poorly understood so far. It is of particular interest to investigate how the variants are incorporated into chromatin and mark specific chromatin states to regulate gene expression, and how they are involved in development and diseases. In this review, we focus on recent progress in studies of epigenetic regulation of three extensively investigated variants including H2A.Z, macroH2A and H3.3, and their functional implications in development and diseases.
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.
