HEB associates with PRC2 and SMAD2/3 to regulate developmental fates

Nature Communications
Se-Jin YoonJulie C Baker

Abstract

In embryonic stem cells, extracellular signals are required to derepress developmental promoters to drive lineage specification, but the proteins involved in connecting extrinsic cues to relaxation of chromatin remain unknown. We demonstrate that the helix-loop-helix (HLH) protein, HEB, directly associates with the Polycomb repressive complex 2 (PRC2) at a subset of developmental promoters, including at genes involved in mesoderm and endoderm specification and at the Hox and Fox gene families. While we show that depletion of HEB does not affect mouse ESCs, it does cause premature differentiation after exposure to Activin. Further, we find that HEB deposition at developmental promoters is dependent upon PRC2 and independent of Nodal, whereas HEB association with SMAD2/3 elements is dependent of Nodal, but independent of PRC2. We suggest that HEB is a fundamental link between Nodal signalling, the derepression of a specific class of poised promoters during differentiation, and lineage specification in mouse ESCs.

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Citations

Apr 13, 2018·Nature Reviews. Molecular Cell Biology·Charles J David, Joan Massagué
Feb 20, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Darrell AndrewsJohn Crean
Aug 28, 2020·Frontiers in Cell and Developmental Biology·Jie Yang, Wei Jiang
Apr 28, 2020·Journal of Bioinformatics and Computational Biology·Nazmus SalehinPierre Osteil
Oct 10, 2018·Scientific Reports·Yuri S OdakaJun Aruga

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