Accéder au contenu
Merck

SETDB1/NSD-dependent H3K9me3/H3K36me3 dual heterochromatin maintains gene expression profiles by bookmarking poised enhancers.

Molecular cell (2022-01-27)
Amandine Barral, Gabrielle Pozo, Lucas Ducrot, Giorgio L Papadopoulos, Sandrine Sauzet, Andrew J Oldfield, Giacomo Cavalli, Jérôme Déjardin
RÉSUMÉ

Gene silencing by heterochromatin plays a crucial role in cell identity. Here, we characterize the localization, the biogenesis, and the function of an atypical heterochromatin, which is simultaneously enriched in the typical H3K9me3 mark and in H3K36me3, a histone mark usually associated with gene expression. We identified thousands of dual regions in mouse embryonic stem (ES) cells that rely on the histone methyltransferases SET domain bifurcated 1 (SETDB1) and nuclear set domain (NSD)-containing proteins to generate H3K9me3 and H3K36me3, respectively. Upon SETDB1 removal, dual domains lose both marks, gain signatures of active enhancers, and come into contact with upregulated genes, suggesting that it might be an important pathway by which genes are controlled by heterochromatin. In differentiated tissues, a subset of these dual domains is destabilized and becomes enriched in active enhancer marks, providing a mechanistic insight into the involvement of heterochromatin in the maintenance of cell identity.

MATÉRIAUX
Référence du produit
Marque
Description du produit

Sigma-Aldrich
IPTG, ≥99% (TLC), ≤0.1% Dioxane
Sigma-Aldrich
Monoclonal Anti-Proliferating Cell Nuclear Antigen antibody produced in mouse, clone PC 10, ascites fluid
Supelco
4-Hydroxytamoxifène, analytical standard, (E) and (Z) isomers (50:50)
Sigma-Aldrich
Anticorps anti-phospho ARN Pol II (Ser5), clone 1H4B6, clone 1H4B6, from rat