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Published on: January 26, 2018
Set2-dependent K36 methylation is regulated by novel intratail interactions within H3
James N Psathas1, Suting Zheng, Song Tan
1Department of Biochemistry and Molecular Biology, Penn State University, University Park, PA 16802, USA.
The histone H3 tail is crucial for regulating gene transcription elongation by influencing Set2 methylation activity. Modifications and structural changes to the H3 tail control methylation dynamics and localization during this process.
Area of Science:
- Molecular Biology
- Epigenetics
- Gene Regulation
Background:
- Posttranslational modifications to histones are critical for gene regulation.
- The specific roles of histone tail residues in transcription are not fully understood.
Purpose of the Study:
- To investigate the requirement of histone H3 N-terminal tail residues for transcription elongation.
- To elucidate the mechanism by which H3 tail influences Set2 methyltransferase activity.
Main Methods:
- Utilized the RNR3 gene as a model system.
- Generated deletions and point mutations in the histone H3 N-terminal tail.
- Assessed K36 methylation by Set2 in vivo and in vitro.
Main Results:
- Deletion or substitution of H3 tail residues impaired K36 methylation by Set2.
- H3 tail is dispensable for Set2 recruitment but essential for its catalytic activity.
- Arginine substitutions preserving tail charge maintained Set2 function.
Conclusions:
- The H3 tail is required for Set2 catalytic activity, not recruitment.
- Intratail interactions, influenced by modifications and structure, regulate Set2 activity.
- These interactions control methylation dynamics and localization during transcription elongation.
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