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Changes in the position and volume of inactive X chromosomes during the G0/G1 transition

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Abstract

In female mammals, each cell silences one X chromosome by converting it into transcriptionally inert heterochromatin. The inactivation is concomitant with epigenetic changes including methylation of specific histone residues and incorporation of macroH2A. Such epigenetic changes may exert influence on the positioning of the inactive X chromosome (Xi) within the nucleus beyond the level of chromatin structure. However, the dynamic positioning of the inactive X chromosome during cell cycle remains unclear. Here, we show that H3K27me3 is a cell-cycle-independent marker for the inactivated X chromosomes in WI38 cells. By utilizing this marker, three types of Xi locations in the nuclei are classified, which are envelope position (associated with envelope), mid-position (between the envelope and nucleolus), and nucleolus position (associated with the nucleolus). Moreover, serial-section analysis revealed that the inactive X chromosomes in the mid-position appear to be sparser and less condensed than those associated with the nuclear envelope or nucleolus. During the transition from G0 to G1 phase, the inactive X chromosomes tend to move from the envelope position to the nucleolus position in WI38 cells. Our results imply a role of chromosome positioning in maintaining the organization of the inactive X chromosomes in different cell phases.

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Abbreviations

CC:

clear-cut

U/DC:

unclear/decondensed chromatin

U/CC:

unclear/condensed chromatin

DAPI:

4′,6-diamidino-2-phenylindole dihydrochloride

H3K9me2:

histone H3 lysine 9 dimethylation

H3K27me3:

histone H3 lysine 27 trimethylation

Xi:

inactivated X chromosome

Xa:

activated X chromosome

Xist:

X-inactivation specific transcript

BrdU:

5′-bromodeoxyuridine

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Acknowledgements

We are very grateful to Prof. Andrew Belmont. The initial work has been done in his laboratory.

Funding

This work was supported by the National Natural Science Foundation of China (No. 91219101, 31471205 and 31571394), the National Basic Research Program of China (973 Program, No. 2013CB530700), a fund granted by Beijing Key Laboratory of Gene Resource and Molecular Development, a fund granted by Key Laboratory for Cell Proliferation and Regulation Biology, Ministry of Education of China, and a fund granted by Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study (No. 0223-0002-0002000-56).

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Contributions

W.T. and Q.L. conceived, designed and supervised the project, and modified the manuscript. T.T. and Q.L. analyzed the data and wrote the paper. G.L. Y.G. L.S. W.T. designed and performed most of the experiments and contributed to the interpretation of results.

Corresponding authors

Correspondence to Qianjin Liang or Wei Tao.

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The authors declare that they have no conflict of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Responsible Editor: Dean A. Jackson

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Lyu, G., Tan, T., Guan, Y. et al. Changes in the position and volume of inactive X chromosomes during the G0/G1 transition. Chromosome Res 26, 179–189 (2018). https://doi.org/10.1007/s10577-018-9577-0

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  • DOI: https://doi.org/10.1007/s10577-018-9577-0

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