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JAZF1-SUZ12 dysregulates PRC2 function and gene expression during cell differentiation
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Tavares, Manuel, Khandelwal, Garima, Muter, Joanne, Viiri, Keijo, Beltran, Manuel, Brosens, Jan J. and Jenner, Richard G. (2022) JAZF1-SUZ12 dysregulates PRC2 function and gene expression during cell differentiation. Cell Reports, 39 (9). 110889. doi:10.1016/j.celrep.2022.110889 ISSN 2211-1247.
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WRAP-JAZF1-SUZ12-dysregulates-PRC2-function-gene-expression-during-cell-differentiation-2022.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (3570Kb) | Preview |
Official URL: https://doi.org/10.1016/j.celrep.2022.110889
Abstract
Polycomb repressive complex 2 (PRC2) methylates histone H3 lysine 27 (H3K27me3) to maintain gene repression and is essential for cell differentiation. In low-grade endometrial stromal sarcoma (LG-ESS), the PRC2 subunit SUZ12 is often fused with the NuA4/TIP60 subunit JAZF1. We show that JAZF1-SUZ12 dysregulates PRC2 composition, genome occupancy, histone modification, gene expression, and cell differentiation. Loss of the SUZ12 N terminus in the fusion protein abrogates interaction with specific PRC2 accessory factors, reduces occupancy at PRC2 target genes, and diminishes H3K27me3. Fusion to JAZF1 increases H4Kac at PRC2 target genes and triggers recruitment to JAZF1 binding sites during cell differentiation. In human endometrial stromal cells, JAZF1-SUZ12 upregulated PRC2 target genes normally activated during decidualization while repressing genes associated with immune clearance, and JAZF1-SUZ12-induced genes were also overexpressed in LG-ESS. These results reveal defects in chromatin regulation, gene expression, and cell differentiation caused by JAZF1-SUZ12 that may underlie its role in oncogenesis.
| Item Type: | Journal Article | ||||||||||||||||||
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| Subjects: | Q Science > QD Chemistry Q Science > QH Natural history R Medicine > RC Internal medicine |
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| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| SWORD Depositor: | Library Publications Router | ||||||||||||||||||
| Library of Congress Subject Headings (LCSH): | Cell differentiation, Gene expression -- Research, Myometrium -- Research, Uterus -- Cancer, Proteins | ||||||||||||||||||
| Journal or Publication Title: | Cell Reports | ||||||||||||||||||
| Publisher: | Elsevier Inc. | ||||||||||||||||||
| ISSN: | 2211-1247 | ||||||||||||||||||
| Official Date: | 31 May 2022 | ||||||||||||||||||
| Dates: |
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| Volume: | 39 | ||||||||||||||||||
| Number: | 9 | ||||||||||||||||||
| Article Number: | 110889 | ||||||||||||||||||
| DOI: | 10.1016/j.celrep.2022.110889 | ||||||||||||||||||
| Status: | Peer Reviewed | ||||||||||||||||||
| Publication Status: | Published | ||||||||||||||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||||||||
| Date of first compliant deposit: | 27 July 2022 | ||||||||||||||||||
| Date of first compliant Open Access: | 28 July 2022 | ||||||||||||||||||
| RIOXX Funder/Project Grant: |
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