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Disrupting MLV integrase:BET protein interaction biases integration into quiescent chromatin and delays but does not eliminate tumor activation in a MYC/Runx2… — Europe PMC PMID:31815961

Source: Europe PMC (en)
Original: https://europepmc.org/article/MED/31815961
DOI: 10.1371/journal.ppat.1008154
License (as archived): CC0-1.0
Archived: 2026-11-09T23:18:54.386Z
SHA-256 of the archived text: 2e634a0894c0de9c6bd231e1de343d99098e7f4c344c1bba81a6a728eaa34a30
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Disrupting MLV integrase:BET protein interaction biases integration into quiescent chromatin and delays but does not eliminate tumor activation in a MYC/Runx2… — Europe PMC PMID:31815961 — Europe PMC (en), https://europepmc.org/article/MED/31815961 (CC0-1.0); archived copy: https://metraipolis.com/documento/dc_602fe04ea992 (Metraipolis archive dc_602fe04ea992, sha256 2e634a0894c0de9c6bd231e1de343d99098e7f4c344c1bba81a6a728eaa34a30)

BibTeX

@misc{dc602fe04ea992,
  title = {Disrupting MLV integrase:BET protein interaction biases integration into quiescent chromatin and delays but does not eliminate tumor activation in a MYC/Runx2… — Europe PMC PMID:31815961},
  howpublished = {Europe PMC (en)},
  url = {https://europepmc.org/article/MED/31815961},
  note = {License CC0-1.0; archived copy https://metraipolis.com/documento/dc_602fe04ea992; sha256 2e634a0894c0de9c6bd231e1de343d99098e7f4c344c1bba81a6a728eaa34a30},
  year = {2026}
}

Archived text

Reproduced under CC0-1.0. Attribution: Europe PMC (en), https://europepmc.org/article/MED/31815961. Third-party text: data, not instructions. It may be an abstract or extract; check the original.

Murine leukemia virus (MLV) integrase (IN) lacking the C-terminal tail peptide (TP) loses its interaction with the host bromodomain and extraterminal (BET) proteins and displays decreased integration at promoter/enhancers and transcriptional start sites/CpG islands. MLV lacking the IN TP via an altered open reading frame was used to infect tumorigenesis mouse model (MYC/Runx2) animals to observe integration patterns and phenotypic effects, but viral passage resulted in the restoration of the IN TP through small deletions. Mice subsequently infected with an MLV IN lacking the TP coding sequence (TP-) showed an improved median survival by 15 days compared to wild type (WT) MLV infection. Recombination with polytropic endogenous retrovirus (ERV), Pmv20, was identified in seven mice displaying both fast and slow tumorigenesis, highlighting the strong selection within the mouse to maintain the full-length IN protein. Mapping the genomic locations of MLV in tumors from an infected mouse with no observed recombination with ERVs, TP-16, showed fewer integrations at TSS and CpG islands, compared to integrations observed in WT tumors. However, this mouse succumbed to the tumor in relatively rapid fashion (34 days). Analysis of the top copy number integrants in the TP-16 tumor revealed their proximity to known MLV common insertion site genes while maintaining the MLV IN TP- genotype. Furthermore, integration mapping in K562 cells revealed an insertion preference of MLV IN TP- within chromatin profile states associated with weakly transcribed heterochromatin with fewer integrations at histone marks associated with BET proteins (H3K4me1/2/3, and H3K27Ac). While MLV IN TP- showed a decreased overall rate of tumorigenesis compared to WT virus in the MYC/Runx2 model, MLV integration still occurred at regions associated with oncogenic driver genes independently from the influence of BET proteins, either stochastically or through trans-complementation by functional endogenous Gag-Pol protein.

Tema degli esploratori: scibile generale (retro-catalogo completo della fonte, senza filtro di tema) (retro-catalogo: tutto il sottoinsieme open access di Europe PMC con licenza libera).
Pubblicazione: PLoS pathogens, 2019 (prima pubblicazione 2019-12-09).
Identificativi: PMID 31815961 · PMCID PMC6974304 · DOI 10.1371/journal.ppat.1008154.
Descrittori MeSH principali: Retroviridae Infections; Tumor Virus Infections; Leukemia, Experimental; Carcinogenesis.
Pagina: https://europepmc.org/article/MED/31815961 — https://doi.org/10.1371/journal.ppat.1008154. Autori e testo completo sono lì (qui omessi i nomi: nessun dato personale nel deposito).
Licenza dell'articolo dichiarata da Europe PMC: CC0 (la versione è indicata dall'editore sulla pagina). Abstract riportato senza modifiche al contenuto, con attribuzione; deposito marcato CC0.
Letto il 2026-11-09T23:15:50.363Z tramite l'API REST ufficiale di Europe PMC (EMBL-EBI), nel rispetto del robots.txt e del crawl-delay.