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MLL-AF4 Spreading Identifies Binding Sites that Are Distinct from Super-Enhancers and that Govern Sensitivity to DOT1L Inhibition in Leukemia.

Abstract:

Understanding the underlying molecular mechanisms of defined cancers is crucial for effective personalized therapies. Translocations of the mixed-lineage leukemia (MLL) gene produce fusion proteins such as MLL-AF4 that disrupt epigenetic pathways and cause poor-prognosis leukemias. Here, we find that at a subset of gene targets, MLL-AF4 binding spreads into the gene body and is associated with the spreading of Menin binding, increased transcription, increased H3K79 methylation (H3K79me2/3), a...

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Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1016/j.celrep.2016.12.054

Authors


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Institution:
University of Oxford
Division:
MPLS
Department:
Engineering Science
Sub department:
Institute of Biomedical Engineering
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Engineering Science
Sub department:
Institute of Biomedical Engineering
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
RDM
Sub department:
Weatherall Insti. of Molecular Medicine
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Engineering Science
Sub department:
Institute of Biomedical Engineering
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Biochemistry
Role:
Author
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National Institute for Health Research More from this funder
UCSF Academic Senate More from this funder
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Publisher:
Cell Press Publisher's website
Journal:
Cell Reports Journal website
Volume:
18
Issue:
2
Pages:
482-495
Publication date:
2017-01-10
Acceptance date:
2016-12-16
DOI:
EISSN:
2211-1247
ISSN:
2211-1247
Source identifiers:
670826
Language:
English
Keywords:
Pubs id:
pubs:670826
UUID:
uuid:757c5208-a4dd-4c3e-9f0a-7480ca10d07c
Local pid:
pubs:670826
Deposit date:
2017-01-17

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