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公開
学術論文

MSL2 ensures biallelic gene expression in mammals

MPS-Authors

Sun,  Yidan
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Wiese,  Meike
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Hmadi,  Raed
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Karayol,  Remzi
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Seyfferth,  Janine
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Greene,  Juan Alfonso Martinez
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Erdogdu,  Niyazi Umut
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Deboutte,  Ward
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Arrigoni,  Laura
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Holz,  Herbert
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Renschler,  Gina
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Hirsch,  Naama
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Foertsch,  Arion
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Basilicata,  Maria Felicia
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Stehle,  Thomas
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Shvedunova,  Maria
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Bella,  Chiara
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Rodrigues,  Cecilia Pessoa
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Manke,  Thomas
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Akhtar,  Asifa
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

External Resource

https://www.nature.com/articles/s41586-023-06781-3
(出版社版)

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フルテキスト (公開)

10.1038_s41586-023-06781-3.pdf
(出版社版), 20MB

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引用

Sun, Y., Wiese, M., Hmadi, R., Karayol, R., Seyfferth, J., Greene, J. A. M., Erdogdu, N. U., Deboutte, W., Arrigoni, L., Holz, H., Renschler, G., Hirsch, N., Foertsch, A., Basilicata, M. F., Stehle, T., Shvedunova, M., Bella, C., Rodrigues, C. P., Schwalb, B., Cramer, P., Manke, T., & Akhtar, A. (2023). MSL2 ensures biallelic gene expression in mammals. Nature. doi:10.1038/s41586-023-06781-3.


引用: https://hdl.handle.net/21.11116/0000-000D-FEDB-F
要旨
In diploid organisms, biallelic gene expression enables the production of adequate levels of mRNA1,2. This is essential for haploinsufficient genes, which require biallelic expression for optimal function to prevent the onset of developmental disorders1,3. Whether and how a biallelic or monoallelic state is determined in a cell-type-specific manner at individual loci remains unclear. MSL2 is known for dosage compensation of the male X chromosome in flies. Here we identify a role of MSL2 in regulating allelic expression in mammals. Allele-specific bulk and single-cell analyses in mouse neural progenitor cells revealed that, in addition to the targets showing biallelic downregulation, a class of genes transitions from biallelic to monoallelic expression after MSL2 loss. Many of these genes are haploinsufficient. In the absence of MSL2, one allele remains active, retaining active histone modifications and transcription factor binding, whereas the other allele is silenced, exhibiting loss of promoter-enhancer contacts and the acquisition of DNA methylation. Msl2-knockout mice show perinatal lethality and heterogeneous phenotypes during embryonic development, supporting a role for MSL2 in regulating gene dosage. The role of MSL2 in preserving biallelic expression of specific dosage-sensitive genes sets the stage for further investigation of other factors that are involved in allelic dosage compensation in mammalian cells, with considerable implications for human disease.