Article
Reporting summary
Further information on research design is available in the Nature
Research Reporting Summary linked to this paper.
Data availability
ChIP-seq, NS-seq, BrdU-seq and RNA-seq data have been deposited
in the Gene Expression Omnibus (GEO) under accession number
GSE134988. Further information and resources and reagents are avail-
able from G.L. upon reasonable request. Source data for Figs. 1, 2, 4,
Extended Data Figs. 1–3, 5–8 and Supplementary Figures are provided
with the paper.
Code availability
Custom codes used for data analysis in this paper can be found at
https://github.com/Leavy-Zhang/RepliCode.
Acknowledgements We thank M. Méchali for advice on nascent-strand sequencing; and B.
Stillman and Z. Zhang for critical reading and discussion of the manuscript. This work was
supported by grants to G.L. from the Ministry of Science and Technology of China
(2017YFA0504202), the National Natural Science Foundation of China (31525013, 31630041
and 31521002), and the Chinese Academy of Sciences (CAS) Strategic Priority Research
Program (XDB19040202). The work was also supported by the CAS Key Research Program on
Frontier Science (QYZDY-SSW-SMC020) and a Howard Hughes Medical Institute (HHMI)
international research scholar grant (55008737) to G.L. This work was also supported by a
grant from the National Natural Science Foundation of China to L.Z. (31801062); the China
Postdoctoral Science Foundation to Z.W. (2019M650871); the Ministry of Science and
Technology of China (2018YFE0203302) and the National Natural Science Foundation of
China (31871290) to P.C.; and the Ministry of Science and Technology of China to J.P.
(2016YFA05023032). All fluorescence imaging data were collected at the Center for Bio-
imaging, Core Facility for Protein Sciences (Institute of Biophysics, CAS). All radioactivity
experiments were performed at the radioactive isotope laboratory (Institute of Biophysics,
CAS), with guidance from H. J. Zhang in handling radioactive materials.Author contributions H.L. carried out experiments and composed the figures. L.Z. performed
bioinformatics analysis of next-generation sequencing data and generated figures. Z.W.
analysed the phenotypic effects of the H2A.Z-knockdown on cell-cycle deficiency, and
assisted with ChIP-seq experiments and the analysis of next-generation sequencing data. M.L.
analysed the phenotype of H2A.Z CKO mice and provided T cells for biochemistry
experiments. W.Z. and H.D. performed mass-spectrometry analysis of the H4K20 modification
of histone methyltransferase products, mononucleosomes in vivo and cells treated with siNC
or siHA.Z oligonucleotides. X.C. and F.Y. performed mass-spectrometry analysis of H2A.Z
nucleosome binding partners. P.Z. and X.W. assisted with the quantification of the histone
methyltransferase reaction, plasmid construction, and protein purification. T.L. and J.P.
performed the in silico analysis of the interaction between H2A.Z and SUV420H1. L.C. assisted
with the analysis of H2A.Z and H4K20me2 sequencing data. C.J. constructed the H2A.Z CKO
mice and assisted with their phenotype analysis. G.W. assisted with plasmid construction and
protein purification. P.C. and R.M. helped to discuss the project. M.Z. conceived the project on
the phenotype of H2A.Z CKO mice. G.L. conceived and supervised the project, analysed the
data and wrote the manuscript.Competing interests The authors declare no competing interests.
Additional information
Supplementary information is available for this paper at https://doi.org/10.1038/s41586-019-
1877-9.
Correspondence and requests for materials should be addressed to M.Z. or G.L.
Reprints and permissions information is available at http://www.nature.com/reprints.