Histone H3 tail binds a unique sensing pocket in EZH2 to activate the PRC2 methyltransferase
Copyright policy )Histone H3 tail binds a unique sensing pocket in EZH2 to activate the PRC2 methyltransferase
Significance Polycomb Repressor Complex 2 (PRC2) is an epigenetic effector enzyme with key roles in gene silencing and establishment of facultative heterochromatin. Mutations of this histone lysine methyltransferase and its substrate H3K27 are linked to multiple human pathologies, and PRC2 has been identified as a therapeutic target in cancer treatment. The H3K27 methylation activity of PRC2 is sensitive to the chromatin environment, including the methylation state of H3K36 on the same histone tail. The mechanistic basis of this negative cross-talk is poorly understood. The present work sheds light on this question by identifying a regulatory feature on the catalytic subunit of PRC2, EZH2, which acts as a specific sensor for H3K36 methylation state. The work reveals an unusual mode of enzyme modulation by a substrate molecule.
- University of Wisconsin–Oshkosh United States
- College of New Jersey United States
- University of Wisconsin–Madison United States
- King's College London United Kingdom
- Wisconsin Institutes for Discovery United States
Models, Molecular, Binding Sites, PRC2 methyltransferase, 500, 540, Chemical biology, Recombinant Proteins, Designer chromatin, Histones, Mutation, Humans, Enhancer of Zeste Homolog 2 Protein, Protein Binding
Models, Molecular, Binding Sites, PRC2 methyltransferase, 500, 540, Chemical biology, Recombinant Proteins, Designer chromatin, Histones, Mutation, Humans, Enhancer of Zeste Homolog 2 Protein, Protein Binding
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).85 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
Citations provided by BIP!Popularity provided by BIP!