MSL2 ensures biallelic gene expression in mammals
Abstract: 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
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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Nature : international weekly journal of science. - 624, 7990 (2023) , 173-181, ISSN: 1476-4687
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
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Universität
- (wann)
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2024
- Urheber
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Sun, Yidan
Wiese, Meike
Hmadi, Raed
Karayol, Remzi
Seyfferth, Janine
Martinez Greene, Juan Alfonso
Erdogdu, Niyazi Umut
Deboutte, Ward
Arrigoni, Laura
Holz, Herbert
Renschler, Gina
Hirsch, Naama
Förtsch, Arion
Basilicata, Maria Felicia
Stehle, Thomas
Shvedunova, Maria
Bella, Chiara
Pessoa Rodrigues, Cecilia
Schwalb, Björn
Cramer, Patrick
Manke, Thomas
Akhtar, Asifa
- DOI
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10.1038/s41586-023-06781-3
- URN
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urn:nbn:de:bsz:25-freidok-2544948
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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15.08.2025, 07:25 MESZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Sun, Yidan
- Wiese, Meike
- Hmadi, Raed
- Karayol, Remzi
- Seyfferth, Janine
- Martinez Greene, Juan Alfonso
- Erdogdu, Niyazi Umut
- Deboutte, Ward
- Arrigoni, Laura
- Holz, Herbert
- Renschler, Gina
- Hirsch, Naama
- Förtsch, Arion
- Basilicata, Maria Felicia
- Stehle, Thomas
- Shvedunova, Maria
- Bella, Chiara
- Pessoa Rodrigues, Cecilia
- Schwalb, Björn
- Cramer, Patrick
- Manke, Thomas
- Akhtar, Asifa
- Universität
Entstanden
- 2024
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