DOI: 10.1073/pnas.0408918102. Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase

Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase

10.1073/pnas.0408918102

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

X inactivation involves the stable silencing of one of the two X chromosomes in XX female mammals. Initiation of this process occurs during early development and involves Xist (X-inactive-specific transcript) RNA coating and the recruitment of Polycomb repressive complex (PRC) 2 and PRC1 proteins. This recruitment results in an inactive state that is initially labile but is further locked in by epigenetic marks such as DNA methylation, histone hypoacetylation, and MACROH2A deposition. Here, we report that the E3 ubiquitin ligase consisting of SPOP and CULLIN3 is able to ubiquitinate the Polycomb group protein BMI1 and the variant histone MACROH2A. We find that in addition to MACROH2A, PRC1 is recruited to the inactivated X chromosome in somatic cells in a highly dynamic, cell cycle-regulated manner. Importantly, RNAi-mediated knock-down of CULLIN3 or SPOP results in loss of MACROH2A1 from the inactivated X chromosome (Xi), leading to reactivation of the Xi in the presence of inhibitors of DNA methylation and histone deacetylation. Likewise, Xi reactivation is also seen on MacroH2A1 RNAi under these conditions. Hence, we propose that the PRC1 complex is involved in the maintenance of X chromosome inactivation in somatic cells. We further demonstrate that MACROH2A1 deposition is regulated by the CULLIN3/SPOP ligase complex and is actively involved in stable X inactivation, likely through the formation of an additional layer of epigenetic silencing.

Bibliography

HernÃ¡ndez-MuÃ±oz, I., Lund, A. H., van der Stoop, P., Boutsma, E., Muijrers, I., Verhoeven, E., Nusinow, D. A., Panning, B., Marahrens, Y., & van Lohuizen, M. (2005). Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase. Proceedings of the National Academy of Sciences, 102(21), 7635â7640.

Authors 10

Inmaculada Hernández-Muñoz (first)
Anders H. Lund (additional)
Petra van der Stoop (additional)
Erwin Boutsma (additional)
Inhua Muijrers (additional)
Els Verhoeven (additional)
Dmitri A. Nusinow (additional)
Barbara Panning (additional)
York Marahrens (additional)
Maarten van Lohuizen (additional)

References 48 Referenced 273

Dates

Type	When
Created	20 years, 3 months ago (May 16, 2005, 8:35 p.m.)
Deposited	3 years, 4 months ago (April 25, 2022, 10:53 p.m.)
Indexed	1 month ago (July 25, 2025, 6:52 a.m.)
Issued	20 years, 3 months ago (May 16, 2005)
Published	20 years, 3 months ago (May 16, 2005)
Published Online	20 years, 3 months ago (May 16, 2005)
Published Print	20 years, 3 months ago (May 24, 2005)

Funders 0

None

BibTeX

@article{Hern_ndez_Mu_oz_2005, title={Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase}, volume={102}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0408918102}, DOI={10.1073/pnas.0408918102}, number={21}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Hernández-Muñoz, Inmaculada and Lund, Anders H. and van der Stoop, Petra and Boutsma, Erwin and Muijrers, Inhua and Verhoeven, Els and Nusinow, Dmitri A. and Panning, Barbara and Marahrens, York and van Lohuizen, Maarten}, year={2005}, month=may, pages={7635–7640} }

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