Targeting Menin disrupts the KMT2A/B and polycomb balance to paradoxically activate bivalent genes (Record no. 2407)
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042 ## - AUTHENTICATION CODE | |
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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. |
500 ## - GENERAL NOTE | |
General note | /pmc/articles/PMC7614190/ |
500 ## - GENERAL NOTE | |
General note | /pubmed/36635503 |
520 ## - SUMMARY, ETC. | |
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. |
540 ## - TERMS GOVERNING USE AND REPRODUCTION NOTE | |
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. |
546 ## - LANGUAGE NOTE | |
Language note | en |
690 ## - LOCAL SUBJECT ADDED ENTRY--TOPICAL TERM (OCLC, RLIN) | |
Topical term or geographic name as entry element | Article |
655 7# - INDEX TERM--GENRE/FORM | |
Genre/form data or focus term | Text |
Source of term | local |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Gillespie, Andrea |
Relator term | author |
9 (RLIN) | 3069 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Gomez, Juliana |
Relator term | author |
9 (RLIN) | 3070 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Kumari, Nishi |
Relator term | author |
9 (RLIN) | 3071 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Motazedian, Ali |
Relator term | author |
9 (RLIN) | 3072 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Chan, Kah Lok |
Relator term | author |
9 (RLIN) | 3073 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Bell, Charles C. |
Relator term | author |
9 (RLIN) | 3074 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Gilan, Omer |
Relator term | author |
9 (RLIN) | 3075 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Chan, Yih-Chih |
Relator term | author |
9 (RLIN) | 3076 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Popp, Sarah |
Relator term | author |
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. |
Relator term | author |
9 (RLIN) | 3082 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Ernst, Patricia |
Relator term | author |
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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