SUMOylation enhances DNMT1 function to repress mega-intergenic RNAs and viral mimicry

Structures of pUG-fold RNA bound to DNMT1 reveal a mechanism for RNA-mediated epigenetic regulation

This study provides the first structural basis for pUG- fold RNA recognition by a protein and illustrates how cryo-EM and AI-based methods for protein and RNA structure prediction synergize to inform the mechanism of RNA-mediated regulation of DNMT1.

MeCP2 functions as a DNA methylation reader in immune homeostasis and cancer

DNA methylation is a key epigenetic mechanism that mediates gene expression and informs cellular identity. Methyl-CpG binding protein 2 (MeCP2) is a protein capable of recognizing and interpreting the methylated DNA code to bring about phenotypic outcomes through co-factor interactions. Altered DNA methylation patterns...

Live-cell DNMT3A “catalysome” mapping using engineered methyl-transfer pathways

Abstract Catalytic interplay among three major DNA methyltransferases (DNMTs) establishes and maintains genomic modification patterns that define mammalian cell identity and transitions during development. Despite extensive molecular characterization, mechanisms and precise contributions of DNMT-specific methylation in...

A feed-forward UHRF1 read-write mechanism supports H3 multi- mono-ubiquitination and DNA methylation maintenance at CpG-sparse regions

LncRNA-mediated organization of oncogenic chromatin state is a targetable vulnerability in leukemia

This study uncovers a therapeutic vulnerable lncRNA-centric circuitry and provides compelling preclinical evidence for the development and application of a novel RNA targeting-LNP based therapy for treatment of myeloid leukemia.

Reassessing the contribution of the histone H3 tail to KRAB–DNMT3L-mediated epigenetic silencing

It is suggested that the engineered H3 tail does not confer a general functional advantage within the KRAB–DNMT3L–dCas9 architecture under the conditions tested.