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  The Transcriptionally Permissive Chromatin State of Embryonic Stem Cells Is Acutely Tuned to Translational Output

Bulut-Karslioglu, A., Macrae, T. A., Oses-Prieto, J. A., Covarrubias, S., Percharde, M., Ku, G., et al. (2018). The Transcriptionally Permissive Chromatin State of Embryonic Stem Cells Is Acutely Tuned to Translational Output. Cell Stem Cell, 22(3): e8, pp. 369-383. doi:10.1016/j.stem.2018.02.004.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0003-4DFE-A Version Permalink: http://hdl.handle.net/21.11116/0000-0003-4DFF-9
Genre: Journal Article

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 Creators:
Bulut-Karslioglu, Aydan1, 2, Author              
Macrae, Trisha A., Author
Oses-Prieto, Juan A. , Author
Covarrubias, Sergio , Author
Percharde, Michelle , Author
Ku, Gregory , Author
Diaz, Aaron , Author
McManus, Michael T. , Author
Burlingame, Alma L. , Author
Ramalho-Santos, Miguel , Author
Affiliations:
1Stem Cell Chromatin (Aydan Bulut-Karslioglu), Dept. of Genome Regulation, (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_3014185              
2Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences and Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA, ou_persistent22              

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Free keywords: Chd1; blastocyst; embryonic stem cells; euchromatin; hypertranscription; mTOR; permissive chromatin; ribosome; translation
 Abstract: A permissive chromatin environment coupled to hypertranscription drives the rapid proliferation of embryonic stem cells (ESCs) and peri-implantation embryos. We carried out a genome-wide screen to systematically dissect the regulation of the euchromatic state of ESCs. The results revealed that cellular growth pathways, most prominently translation, perpetuate the euchromatic state and hypertranscription of ESCs. Acute inhibition of translation rapidly depletes euchromatic marks in mouse ESCs and blastocysts, concurrent with delocalization of RNA polymerase II and reduction in nascent transcription. Translation inhibition promotes rewiring of chromatin accessibility, which decreases at a subset of active developmental enhancers and increases at histone genes and transposable elements. Proteome-scale analyses revealed that several euchromatin regulators are unstable proteins and continuously depend on a high translational output. We propose that this mechanistic interdependence of euchromatin, transcription, and translation sets the pace of proliferation at peri-implantation and may be employed by other stem/progenitor cells.

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Language(s): eng - English
 Dates: 2018-02-072018-03-01
 Publication Status: Published online
 Pages: -
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 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1016/j.stem.2018.02.004
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Title: Cell Stem Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: 15 Volume / Issue: 22 (3) Sequence Number: e8 Start / End Page: 369 - 383 Identifier: ISSN: 1934-5909
CoNE: https://pure.mpg.de/cone/journals/resource/1934-5909