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The histone H4 basic patch regulates SAGA-mediated H2B deubiquitination and histone acetylation
Hashem A Meriesh1, Andrew M Lerner1, Mahesh B Chandrasekharan2
1Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599.
The Journal of Biological Chemistry
|April 5, 2020
Summary
The histone H4 basic patch regulates histone H2B monoubiquitylation (H2Bub1) levels by controlling deubiquitination. This finding reveals a novel regulatory mechanism for H2Bub1, impacting DNA processes.
Area of Science:
- * Epigenetics and Chromatin Biology
- * Molecular Biology
- * Yeast Genetics
Background:
- * Histone H2B monoubiquitylation (H2Bub1) is crucial for gene transcription, DNA repair, and replication.
- * H2Bub1 also mediates trans-histone regulation of H3K4 and H3K79 methylation.
- * The precise regulation of H2Bub1 levels remains incompletely understood.
Purpose of the Study:
- * To investigate the role of the histone H4 basic patch in regulating H2Bub1.
- * To elucidate the mechanisms by which the H4 basic patch influences H2Bub1 dynamics.
- * To explore the functional consequences of H4 basic patch mutations on chromatin modifications.
Main Methods:
- * Analysis of H2Bub1 levels in yeast strains with mutations in the H4 basic patch (H42RA).
- * Assessment of chemotoxin sensitivities in mutant strains.
- * Utilization of an optogenetic tool to control the localization of the H2Bub1 E3 ligase (Bre1) for in vivo ubiquitylation and deubiquitination kinetic studies.
- * Investigation of the impact of H4 mutations on the activity of deubiquitinases (Ubp8, Ubp10) and histone acetylation.
Main Results:
- * Yeast cells with H4 basic patch mutations (H42RA) showed a significant reduction in global H2Bub1 levels.
- * H42RA mutants exhibited chemotoxin sensitivities, indicating impaired DNA-templated processes.
- * The H4 basic patch regulates H2Bub1 levels independently of chromatin remodelers and H3K79 methylation.
- * Bre1's ubiquitylation activity was unaffected, but H2Bub1 deubiquitination by SAGA-associated Ubp8 increased in H42RA mutants.
- * Increased SAGA-mediated histone acetylation was observed in H4 basic patch mutants.
Conclusions:
- * The histone H4 basic patch plays a regulatory role in controlling H2Bub1 levels.
- * This regulation occurs primarily through modulation of H2Bub1 deubiquitination by Ubp8 within the SAGA complex.
- * The H4 basic patch is a key regulator of SAGA-mediated histone modifications, impacting chromatin function.
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