MLL-ENL inhibits polycomb repressive complex 1 to achieve efficient transformation of hematopoietic cells
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F13%3A33153688" target="_blank" >RIV/61989592:15110/13:33153688 - isvavai.cz</a>
Result on the web
<a href="http://www.sciencedirect.com/science/article/pii/S2211124713001629" target="_blank" >http://www.sciencedirect.com/science/article/pii/S2211124713001629</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.celrep.2013.03.038" target="_blank" >10.1016/j.celrep.2013.03.038</a>
Alternative languages
Result language
angličtina
Original language name
MLL-ENL inhibits polycomb repressive complex 1 to achieve efficient transformation of hematopoietic cells
Original language description
Stimulation of transcriptional elongation is a key activity of leukemogenic MLL fusion proteins. Here, we provide evidence that MLL-ENL also inhibits Polycomb-mediated silencing as a prerequisite for efficient transformation. Biochemical studies identified ENL as a scaffold that contacted the elongation machinery as well as the Polycomb repressive complex 1 (PRC1) component CBX8. These interactions were mutually exclusive in vitro, corresponding to an antagonistic behavior of MLL-ENL and CBX8 in vivo. CBX8 inhibited elongation in a specific reporter assay, and this effect was neutralized by direct association with ENL. Correspondingly, CBX8-binding-defective MLL-ENL could not fully activate gene loci necessary for transformation. Finally, we demonstrate dimerization of MLL-ENL as a neomorphic activity that may augment Polycomb inhibition and transformation.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
FD - Oncology and haematology
OECD FORD branch
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Result continuities
Project
<a href="/en/project/2B06077" target="_blank" >2B06077: High throughput analysis of chromatin structure for development of novel diagnostic and therapeutic approaches in cancer.</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>Z - Vyzkumny zamer (s odkazem do CEZ)<br>S - Specificky vyzkum na vysokych skolach
Others
Publication year
2013
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cell Reports
ISSN
2211-1247
e-ISSN
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Volume of the periodical
3
Issue of the periodical within the volume
5
Country of publishing house
US - UNITED STATES
Number of pages
14
Pages from-to
1553-1566
UT code for WoS article
000321899300026
EID of the result in the Scopus database
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