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  The implication of early chromatin changes in X chromosome inactivation.

Zylicz, J. J., Bousard, A., Zumer, K., Dossin, F., Mohammad, E., da Rocha, S. T., et al. (2019). The implication of early chromatin changes in X chromosome inactivation. Cell, 176(1-2), 182-197. doi:10.1016/j.cell.2018.11.041.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0002-B85F-5 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-C24E-B
Genre: Journal Article

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Zylicz, J. J., Author
Bousard, A., Author
Zumer, K.1, Author              
Dossin, F., Author
Mohammad, E., Author
da Rocha, S. T., Author
Schwalb, B.1, Author              
Syx, L., Author
Dingli, F., Author
Loew, D., Author
Cramer, P.1, Author              
Heard, E., Author
Affiliations:
1Department of Molecular Biology, MPI for Biophysical Chemistry, Max Planck Society, ou_1863498              

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 Abstract: During development, the precise relationships between transcription and chromatin modifications often remain unclear. We use the X chromosome inactivation (XCI) paradigm to explore the implication of chromatin changes in gene silencing. Using female mouse embryonic stem cells, we initiate XCI by inducing Xist and then monitor the temporal changes in transcription and chromatin by allele-specific profiling. This reveals histone deacetylation and H2AK119 ubiquitination as the earliest chromatin alterations during XCI. We show that HDAC3 is pre-bound on the X chromosome and that, upon Xist coating, its activity is required for efficient gene silencing. We also reveal that first PRC1-associated H2AK119Ub and then PRC2-associated H3K27me3 accumulate initially at large intergenic domains that can then spread into genes only in the context of histone deacetylation and gene silencing. Our results reveal the hierarchy of chromatin events during the initiation of XCI and identify key roles for chromatin in the early steps of transcriptional silencing

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Language(s): eng - English
 Dates: 2018-12-212019-01-10
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1016/j.cell.2018.11.041
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Title: Cell
Source Genre: Journal
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Pages: - Volume / Issue: 176 (1-2) Sequence Number: - Start / End Page: 182 - 197 Identifier: -