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Article Dans Une Revue (Data Paper) eLife Année : 2019

Dynamic enhancer partitioning instructs activation of a growth-related gene during exit from naïve pluripotency

Maxim Greenberg
Aurélie Teissandier
  • Fonction : Auteur
Marius Walter
  • Fonction : Auteur
Daan Noordermeer
Deborah Bourc'His
  • Fonction : Auteur
  • PersonId : 1215490

Résumé

During early mammalian development, the chromatin landscape undergoes profound transitions. The Zdbf2 gene—involved in growth control—provides a valuable model to study this window: upon exit from naïve pluripotency and prior to tissue differentiation, it undergoes a switch from a distal to a proximal promoter usage, accompanied by a switch from polycomb to DNA methylation occupancy. Using a mouse embryonic stem cell (ESC) system to mimic this period, we show here that four enhancers contribute to the Zdbf2 promoter switch, concomitantly with dynamic changes in chromatin architecture. In ESCs, the locus is partitioned to facilitate enhancer contacts with the distal Zdbf2 promoter. Relieving the partition enhances proximal Zdbf2 promoter activity, as observed during differentiation or with genetic mutants. Importantly, we show that 3D regulation occurs upstream of the polycomb and DNA methylation pathways. Our study reveals the importance of multi-layered regulatory frameworks to ensure proper spatio-temporal activation of developmentally important genes.

Dates et versions

hal-03939280 , version 1 (14-01-2023)

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Maxim Greenberg, Aurélie Teissandier, Marius Walter, Daan Noordermeer, Deborah Bourc'His. Dynamic enhancer partitioning instructs activation of a growth-related gene during exit from naïve pluripotency. eLife, 2019, 8, ⟨10.7554/eLife.44057⟩. ⟨hal-03939280⟩
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