SAFB restricts contact domain boundaries associated with L1 chimeric transcription.
Mol Cell
; 84(9): 1637-1650.e10, 2024 May 02.
Article
em En
| MEDLINE
| ID: mdl-38604171
ABSTRACT
Long interspersed element-1 (LINE-1 or L1) comprises 17% of the human genome, continuously generates genetic variations, and causes disease in certain cases. However, the regulation and function of L1 remain poorly understood. Here, we uncover that L1 can enrich RNA polymerase IIs (RNA Pol IIs), express L1 chimeric transcripts, and create contact domain boundaries in human cells. This impact of L1 is restricted by a nuclear matrix protein scaffold attachment factor B (SAFB) that recognizes transcriptionally active L1s by binding L1 transcripts to inhibit RNA Pol II enrichment. Acute inhibition of RNA Pol II transcription abolishes the domain boundaries associated with L1 chimeric transcripts, indicating a transcription-dependent mechanism. Deleting L1 impairs domain boundary formation, and L1 insertions during evolution have introduced species-specific domain boundaries. Our data show that L1 can create RNA Pol II-enriched regions that alter genome organization and that SAFB regulates L1 and RNA Pol II activity to preserve gene regulation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
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RNA Polimerase II
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Receptores de Estrogênio
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Elementos Nucleotídeos Longos e Dispersos
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Proteínas de Ligação à Região de Interação com a Matriz
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article