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Verfasst von:Boulard, Mathieu [VerfasserIn]   i
 Rucli, Sofia [VerfasserIn]   i
 Edwards, John R. [VerfasserIn]   i
 Bestor, Timothy H. [VerfasserIn]   i
Titel:Methylation-directed glycosylation of chromatin factors represses retrotransposon promoters
Verf.angabe:Mathieu Boulard, Sofia Rucli, John R. Edwards, and Timothy H. Bestor
E-Jahr:2020
Jahr:June 10, 2020
Umfang:7 S.
Fussnoten:Gesehen am 14.08.2020
Titel Quelle:Enthalten in: National Academy of Sciences (Washington, DC)Proceedings of the National Academy of Sciences of the United States of America
Ort Quelle:Washington, DC : National Acad. of Sciences, 1915
Jahr Quelle:2020
Band/Heft Quelle:117(2020), 25, Seite 14292-14298
ISSN Quelle:1091-6490
Abstract:The mechanisms by which methylated mammalian promoters are transcriptionally silenced even in the presence of all of the factors required for their expression have long been a major unresolved issue in the field of epigenetics. Repression requires the assembly of a methylation-dependent silencing complex that contains the TRIM28 protein (also known as KAP1 and TIF1 beta), a scaffolding protein without intrinsic repressive or DNA-binding properties. The identity of the key effector within this complex that represses transcription is unknown. We developed a methylation-sensitized interaction screen which revealed that TRIM28 was complexed with O-linked beta-N-acetylglucosamine transferase (OGT) only in cells that had normal genomic methylation patterns. OGT is the only glycosyltransferase that modifies cytoplasmic and nuclear protein by transfer of N-acetylglucosamine (O-GlcNAc) to serine and threonine hydroxyls. Whole-genome analysis showed that O-glycosylated proteins and TRIM28 were specifically bound to promoters of active retrotransposons and to imprinting control regions, the two major regulatory sequences controlled by DNA methylation. Furthermore, genome-wide loss of DNA methylation caused a loss of O-GlcNAc from multiple transcriptional repressor proteins associated with TRIM28. A newly developed Cas9-based editing method for targeted removal of O-GlcNAc was directed against retrotransposon promoters. Local chromatin de-GlcNAcylation specifically reactivated the expression of the targeted retrotransposon family without loss of DNA methylation. These data revealed that O-linked glycosylation of chromatin factors is essential for the transcriptional repression of methylated retrotransposons.
DOI:doi:10.1073/pnas.1912074117
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1073/pnas.1912074117
 DOI: https://doi.org/10.1073/pnas.1912074117
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:complex
 dna methylation
 DNA methylation
 endogenous retroviruses
 expression
 gene silencing
 in-vitro
 interacts
 o-glcnac transferase
 protein O-glycosylation
 replication
 sequence
 transcription
K10plus-PPN:1727046242
Verknüpfungen:→ Zeitschrift

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