FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2593359096> ?p ?o ?g. }

• W2593359096 endingPage "269" @default.
• W2593359096 startingPage "265" @default.
• W2593359096 abstract "The chromatin-reader protein ENL regulates oncogenic programs in acute myeloid leukaemia by binding via its YEATS domain to acetylated histones on the promoters of actively transcribed genes and recruiting the transcriptional machinery. Cancer cells often exploit transcription machinery and chromatin regulatory pathways to activate oncogenic gene expression programs. Chromatin regulatory mechanisms such as the recognition of modified histones by 'reader' proteins are therefore being explored as potential therapeutic targets in cancer. Here, Xiaobing Shi and colleagues show that ENL is a chromatin reader protein that regulates oncogenic programs in acute myeloid leukaemia (AML). It binds via its YEATS domain to acetylated histones on the promoters of actively transcribed genes and links to the transcriptional machinery. Depletion of ENL leads to anti-leukaemic effects, indicating that disrupting the interaction between the ENL YEATS domain and acetylated histones could be a potential therapeutic approach for AML, either alone or in combination with BET inhibitors. A related paper in this week's issue of Nature from James Bradner and colleagues provides further insights into the role of ENL in leukaemia. Cancer cells are characterized by aberrant epigenetic landscapes and often exploit chromatin machinery to activate oncogenic gene expression programs1. Recognition of modified histones by ‘reader’ proteins constitutes a key mechanism underlying these processes; therefore, targeting such pathways holds clinical promise, as exemplified by the development of bromodomain and extra-terminal (BET) inhibitors2,3. We recently identified the YEATS domain as an acetyl-lysine-binding module4, but its functional importance in human cancer remains unknown. Here we show that the YEATS domain-containing protein ENL, but not its paralogue AF9, is required for disease maintenance in acute myeloid leukaemia. CRISPR–Cas9-mediated depletion of ENL led to anti-leukaemic effects, including increased terminal myeloid differentiation and suppression of leukaemia growth in vitro and in vivo. Biochemical and crystal structural studies and chromatin-immunoprecipitation followed by sequencing analyses revealed that ENL binds to acetylated histone H3, and co-localizes with H3K27ac and H3K9ac on the promoters of actively transcribed genes that are essential for leukaemia. Disrupting the interaction between the YEATS domain and histone acetylation via structure-based mutagenesis reduced the recruitment of RNA polymerase II to ENL-target genes, leading to the suppression of oncogenic gene expression programs. Notably, disrupting the functionality of ENL further sensitized leukaemia cells to BET inhibitors. Together, our data identify ENL as a histone acetylation reader that regulates oncogenic transcriptional programs in acute myeloid leukaemia, and suggest that displacement of ENL from chromatin may be a promising epigenetic therapy, alone or in combination with BET inhibitors, for aggressive leukaemia." @default.
• W2593359096 created "2017-03-16" @default.
• W2593359096 creator A5000432967 @default.
• W2593359096 creator A5005103689 @default.
• W2593359096 creator A5008134007 @default.
• W2593359096 creator A5010972843 @default.
• W2593359096 creator A5012181949 @default.
• W2593359096 creator A5012956545 @default.
• W2593359096 creator A5022689477 @default.
• W2593359096 creator A5025638264 @default.
• W2593359096 creator A5037777156 @default.
• W2593359096 creator A5039409146 @default.
• W2593359096 creator A5042079141 @default.
• W2593359096 creator A5052967210 @default.
• W2593359096 creator A5061571458 @default.
• W2593359096 creator A5078568246 @default.
• W2593359096 creator A5082133407 @default.
• W2593359096 creator A5085032833 @default.
• W2593359096 creator A5087995179 @default.
• W2593359096 creator A5089868970 @default.
• W2593359096 date "2017-03-01" @default.
• W2593359096 modified "2023-10-12" @default.
• W2593359096 title "ENL links histone acetylation to oncogenic gene expression in acute myeloid leukaemia" @default.
• W2593359096 cites W1970309962 @default.
• W2593359096 cites W1976033223 @default.
• W2593359096 cites W1992127633 @default.
• W2593359096 cites W1993275211 @default.
• W2593359096 cites W2003872705 @default.
• W2593359096 cites W2017909805 @default.
• W2593359096 cites W2022936085 @default.
• W2593359096 cites W2026576443 @default.
• W2593359096 cites W2041535798 @default.
• W2593359096 cites W2050236645 @default.
• W2593359096 cites W2057228860 @default.
• W2593359096 cites W2063738914 @default.
• W2593359096 cites W2069918359 @default.
• W2593359096 cites W2073652391 @default.
• W2593359096 cites W2075756021 @default.
• W2593359096 cites W2097065948 @default.
• W2593359096 cites W2130410032 @default.
• W2593359096 cites W2134526812 @default.
• W2593359096 cites W2147138024 @default.
• W2593359096 cites W2162520885 @default.
• W2593359096 cites W2168303063 @default.
• W2593359096 cites W2171426529 @default.
• W2593359096 cites W2171808845 @default.
• W2593359096 cites W2179438025 @default.
• W2593359096 cites W2187898585 @default.
• W2593359096 cites W2205700110 @default.
• W2593359096 cites W2223549218 @default.
• W2593359096 doi "https://doi.org/10.1038/nature21687" @default.
• W2593359096 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5372383" @default.
• W2593359096 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28241141" @default.
• W2593359096 hasPublicationYear "2017" @default.
• W2593359096 type Work @default.
• W2593359096 sameAs 2593359096 @default.
• W2593359096 citedByCount "184" @default.
• W2593359096 countsByYear W25933590962017 @default.
• W2593359096 countsByYear W25933590962018 @default.
• W2593359096 countsByYear W25933590962019 @default.
• W2593359096 countsByYear W25933590962020 @default.
• W2593359096 countsByYear W25933590962021 @default.
• W2593359096 countsByYear W25933590962022 @default.
• W2593359096 countsByYear W25933590962023 @default.
• W2593359096 crossrefType "journal-article" @default.
• W2593359096 hasAuthorship W2593359096A5000432967 @default.
• W2593359096 hasAuthorship W2593359096A5005103689 @default.
• W2593359096 hasAuthorship W2593359096A5008134007 @default.
• W2593359096 hasAuthorship W2593359096A5010972843 @default.
• W2593359096 hasAuthorship W2593359096A5012181949 @default.
• W2593359096 hasAuthorship W2593359096A5012956545 @default.
• W2593359096 hasAuthorship W2593359096A5022689477 @default.
• W2593359096 hasAuthorship W2593359096A5025638264 @default.
• W2593359096 hasAuthorship W2593359096A5037777156 @default.
• W2593359096 hasAuthorship W2593359096A5039409146 @default.
• W2593359096 hasAuthorship W2593359096A5042079141 @default.
• W2593359096 hasAuthorship W2593359096A5052967210 @default.
• W2593359096 hasAuthorship W2593359096A5061571458 @default.
• W2593359096 hasAuthorship W2593359096A5078568246 @default.
• W2593359096 hasAuthorship W2593359096A5082133407 @default.
• W2593359096 hasAuthorship W2593359096A5085032833 @default.
• W2593359096 hasAuthorship W2593359096A5087995179 @default.
• W2593359096 hasAuthorship W2593359096A5089868970 @default.
• W2593359096 hasBestOaLocation W25933590962 @default.
• W2593359096 hasConcept C104317684 @default.
• W2593359096 hasConcept C119157956 @default.
• W2593359096 hasConcept C165864922 @default.
• W2593359096 hasConcept C167227067 @default.
• W2593359096 hasConcept C41091548 @default.
• W2593359096 hasConcept C502942594 @default.
• W2593359096 hasConcept C54355233 @default.
• W2593359096 hasConcept C56952853 @default.
• W2593359096 hasConcept C64927066 @default.
• W2593359096 hasConcept C70721500 @default.
• W2593359096 hasConcept C74401373 @default.
• W2593359096 hasConcept C83640560 @default.
• W2593359096 hasConcept C86339819 @default.
• W2593359096 hasConcept C86803240 @default.

• next