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  Chd1 protects genome integrity at promoters to sustain hypertranscription in embryonic stem cells

Bulut-Karslioglu, A., Jin, H., Kim, Y.-K., Cho, B., Guzman-Ayala, M., Williamson, A. J. K., et al. (2021). Chd1 protects genome integrity at promoters to sustain hypertranscription in embryonic stem cells. Nature Communications, 12: 4859. doi:10.1038/s41467-021-25088-3.

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 Creators:
Bulut-Karslioglu, Aydan1, Author           
Jin, Hu, Author
Kim, Yun-Kyo , Author
Cho, Brandon, Author
Guzman-Ayala, Marcela, Author
Williamson, Andrew J. K. , Author
Hejna, Miroslav , Author
Stötzel, Maximilian1, Author           
Whetton, Anthony D. , Author
Song, Jun S. , Author
Ramalho-Santos, Miguel , Author
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1Stem Cell Chromatin (Aydan Bulut-Karslioglu), Dept. of Genome Regulation, (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_3014185              

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 Abstract: Stem and progenitor cells undergo a global elevation of nascent transcription, or hyper- transcription, during key developmental transitions involving rapid cell proliferation. The chromatin remodeler Chd1 mediates hypertranscription in pluripotent cells but its mechanism of action remains poorly understood. Here we report a novel role for Chd1 in protecting genome integrity at promoter regions by preventing DNA double-stranded break (DSB) accumulation in ES cells. Chd1 interacts with several DNA repair factors including Atm, Parp1, Kap1 and Topoisomerase 2βand its absence leads to an accumulation of DSBs at Chd1-bound Pol II-transcribed genes and rDNA. Genes prone to DNA breaks in Chd1 KO ES cells are longer genes with GC-rich promoters, a more labile nucleosomal structure and roles in chromatin regulation, transcription and signaling. These results reveal a vulnerability of hypertranscribing stem cells to accumulation of endogenous DNA breaks, with important implications for developmental and cancer biology.

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Language(s): eng - English
 Dates: 2021-07-202021-08-11
 Publication Status: Published online
 Pages: -
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 Rev. Type: -
 Identifiers: DOI: 10.1038/s41467-021-25088-3
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Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 12 Sequence Number: 4859 Start / End Page: - Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723