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Publication

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

Cell stem cell | 2018

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.

Pubmed ID: 29499153 RIS Download

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Associated grants

Agency: NIGMS NIH HHS, United States
Id: P41 GM103481
Agency: NIDDK NIH HHS, United States
Id: P30 DK063720
Agency: NIGMS NIH HHS, United States
Id: T32 GM007618
Agency: NIH HHS, United States
Id: S10 OD016229
Agency: NCI NIH HHS, United States
Id: P30 CA082103
Agency: NIGMS NIH HHS, United States
Id: R01 GM123556
Agency: NIGMS NIH HHS, United States
Id: R01 GM113014
Agency: NIMH NIH HHS, United States
Id: U01 MH105028
Agency: Medical Research Council, United Kingdom
Id: MC_UP_1605/4
Agency: NIH HHS, United States
Id: R01 OD012204
Agency: NICHD NIH HHS, United States
Id: F30 HD093116

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