A small UTX stabilization domain of Trr is conserved within mammalian MLL3-4/COMPASS and is sufficient to rescue loss of viability in null animals
Ontology highlight
ABSTRACT: Catalytic-inactivating mutations within the Drosophila enhancer H3K4 monomethyltransferase Trr and its mammalian homologs, MLL3/4, cause only minor changes in gene expression compared to whole-gene deletions for these COMPASS members. To identify essential histone methylatransferase-independent functions of Trr, we screened to identify a minimal Trr domain sufficient to rescue Trr-null lethality and demonstrate that this domain binds and stabilizes Utx in vivo. Using the homologous MLL3/MLL4 human sequences, we mapped a short ~80 amino acid UTX-Stabilization-Domain (USD) that promotes UTX stability in the absence of the rest of MLL3/4. Nuclear UTX stability is enhanced when the USD is fused with the MLL4 HMG-box. Thus, COMPASS-dependent UTX stabilization is an essential non-catalytic function of Trr/MLL3/MLL4, suggesting that stabilizing UTX could be a therapeutic strategy for cancers with MLL3/4 loss-of-function mutations.
ORGANISM(S): Homo sapiens
PROVIDER: GSE158672 | GEO | 2020/10/08
REPOSITORIES: GEO
ACCESS DATA