JOM KITA KE POLITEKNIK

Targeting Menin disrupts the KMT2A/B and polycomb balance to paradoxically activate bivalent genes (Record no. 2205)

MARC details
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Authentication code dc
100 10 - MAIN ENTRY--PERSONAL NAME
Personal name Sparbier, Christina E.
Relator term author
9 (RLIN) 3068
245 00 - TITLE STATEMENT
Title Targeting Menin disrupts the KMT2A/B and polycomb balance to paradoxically activate bivalent genes
260 ## - PUBLICATION, DISTRIBUTION, ETC.
Date of publication, distribution, etc. 2023-02.
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General note /pmc/articles/PMC7614190/
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General note /pubmed/36635503
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Summary, etc. Precise control of activating H3K4me3 and repressive H3K27me3 histone modifications at bivalent promoters is essential for normal development and is frequently corrupted in cancer. By coupling a cell surface readout of bivalent MHC class I gene expression with whole genome CRISPR/Cas9 screens, we identify specific roles for MTF2-PRC2.1, PCGF1-PRC1.1 and Menin-KMT2A/B complexes in maintaining bivalency. Unexpectedly, genetic loss or pharmacological inhibition of Menin phenocopies the effects of polycomb disruption, resulting in derepression of bivalent genes in both cancer cells and pluripotent stem cells. Whilst Menin and KMT2A/B contribute to H3K4me3 at active genes, a separate Menin-independent function of KMT2A/B maintains H3K4me3 and opposes polycomb-mediated repression at bivalent genes. Release of KMT2A from active genes following Menin targeting alters the balance of polycomb and KMT2A at bivalent genes, facilitating gene activation. This functional partitioning of Menin-KMT2A/B complex components reveals therapeutic opportunities that can be leveraged through inhibition of Menin.
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Terms governing use and reproduction
540 ## - TERMS GOVERNING USE AND REPRODUCTION NOTE
Terms governing use and reproduction https://creativecommons.org/licenses/by/4.0/This work is licensed under a CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/) International license.
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Language note en
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Topical term or geographic name as entry element Article
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Genre/form data or focus term Text
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Personal name Gillespie, Andrea
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9 (RLIN) 3069
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Gomez, Juliana
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9 (RLIN) 3070
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Kumari, Nishi
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9 (RLIN) 3071
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Motazedian, Ali
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9 (RLIN) 3072
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Chan, Kah Lok
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9 (RLIN) 3073
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Bell, Charles C.
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9 (RLIN) 3074
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Gilan, Omer
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9 (RLIN) 3075
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Chan, Yih-Chih
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9 (RLIN) 3076
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Popp, Sarah
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9 (RLIN) 3077
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Gough, Daniel J.
Relator term author
9 (RLIN) 3078
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Eckersley-Maslin, Melanie A.
Relator term author
9 (RLIN) 3079
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Dawson, Sarah-Jane
Relator term author
9 (RLIN) 3080
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Lehner, Paul J.
Relator term author
9 (RLIN) 3081
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Sutherland, Kate D.
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9 (RLIN) 3082
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Ernst, Patricia
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9 (RLIN) 3083
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name McGeehan, Gerard M.
Relator term author
9 (RLIN) 3084
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Lam, Enid Y. N.
Relator term author
9 (RLIN) 3085
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Burr, Marian L.
Relator term author
9 (RLIN) 3086
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Dawson, Mark A.
Relator term author
9 (RLIN) 3087
786 0# - DATA SOURCE ENTRY
Note Nat Cell Biol
856 41 - ELECTRONIC LOCATION AND ACCESS
Uniform Resource Identifier <a href="http://dx.doi.org/10.1038/s41556-022-01056-x">http://dx.doi.org/10.1038/s41556-022-01056-x</a>
Public note Connect to this object online.

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