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  The Polycomb-Dependent Epigenome Controls β Cell Cysfunction, Dedifferentiation, and Diabetes

Lu, T.-T.-H., Heyne, S., Dror, E., Casas, E., Leonhardt, L., Boenke, T., et al. (2018). The Polycomb-Dependent Epigenome Controls β Cell Cysfunction, Dedifferentiation, and Diabetes. Cell Metabolism, 15, 1294-1308. doi:doi.org/10.1016/j.cmet.2018.04.013.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0001-F751-D Version Permalink: http://hdl.handle.net/21.11116/0000-0004-EB1A-7
Genre: Journal Article

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 Creators:
Lu, Tess Tsai-Hsiu1, Author
Heyne, Steffen1, Author
Dror, Erez1, Author
Casas, Eduard2, Author
Leonhardt, Laura1, Author
Boenke, Thorina1, Author
Yang, Chih-Hsiang1, Author
Sagar, Sagar1, Author
Arrigoni, Laura1, Author
Dalgaard, Kevin1, Author
Teperino, Raffaele1, Author
Enders, Lennart1, Author
Selvaraj, Madhan1, Author
Ruf, Marius1, Author
Raja, Sunil J.1, Author
Xie, Huafeng2, Author
Boenisch, Ulrike1, Author
Orkin, Stuart H.2, Author
Lynn, Francis C.2, Author
Hoffman, Brad G.2, Author
Grün, Dominic1, Author              Vavouri, Tanya2, AuthorLempradl, Adelheid M.1, AuthorPospisilik, John Andrew1, Author               more..
Affiliations:
1Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, 79108 Freiburg, DE, ou_2243640              
2External Organizations, ou_persistent22              

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 Abstract: To date, it remains largely unclear to what extent chromatin machinery contributes to the susceptibility and progression of complex diseases. Here, we combine deep epigenome mapping with single-cell transcriptomics to mine for evidence of chromatin dysregulation in type 2 diabetes. We find two chromatin-state signatures that track β cell dysfunction in mice and humans: ectopic activation of bivalent Polycomb-silenced domains and loss of expression at an epigenomically unique class of lineage-defining genes. β cell-specific Polycomb (Eed/PRC2) loss of function in mice triggers diabetes-mimicking transcriptional signatures and highly penetrant, hyperglycemia-independent dedifferentiation, indicating that PRC2 dysregulation contributes to disease. The work provides novel resources for exploring β cell transcriptional regulation and identifies PRC2 as necessary for long-term maintenance of β cell identity. Importantly, the data suggest a two-hit (chromatin and hyperglycemia) model for loss of β cell identity in diabetes.

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Language(s): eng - English
 Dates: 2018
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: Cell Metabolism
  Other : Cell Metabolism
Source Genre: Journal
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Publ. Info: Cambridge, MA : Cell Press
Pages: - Volume / Issue: 15 Sequence Number: - Start / End Page: 1294 - 1308 Identifier: ISSN: 1550-4131
CoNE: https://pure.mpg.de/cone/journals/resource/111088195284928