Role of DPPA2 and 4 in chromatin bivalency and multi-lineage commitment

Title	Role of DPPA2 and 4 in chromatin bivalency and multi-lineage commitment
Acronym	DPPAcommit
Start date	2021-01-01
End date	2025-12-31
Sponsor	Gustave Roussy
Institution	Wolf Reik Lab

Associated cell lines

• CAMe001-A (HNES-1, HNES1)
• CAMe002-A (HNES-3, HNES3)
• WAe009-A (H9, WA09)

Project Description

Dppa2 and 4 are small chromatin bound proteins exclusively expressed during pluripotency in mouse. We found that they are needed in mouse ESCs to target bivalency (H3K4me3 and H3K27me3) to a subset of bivalent promoters. In the absence of Dppa2 and 4 bivalency and chromatin accessibility is lost, and DNA methylation gained, and developmental genes fail to be expressed during differentiation (https://www.biorxiv.org/content/10.1101/832873v1, Nature Structural and Molecular Biology, in press). DPPA2 and 4 are conserved in human and in this project we propose to characterise their expression and their role in human pluripotency and differentiation. DPPA2 and 4 will be deleted in hESCs by Crispr/Cas9 targeting, and transcriptional and epigenetic properties of the cells will be studied during the pluripotent state and during in vitro differentiation.