2-Hydroxyisobutyrylation on histone H4K8 is regulated by glucose homeostasis in Saccharomyces cerevisiae

New types of modifications of histones keep emerging. Recently, histone H4K8 2-hydroxyisobutyrylation (H4K8hib) was identified as an evolutionarily conserved modification. However, how this modification is regulated within a cell is still elusive, and the enzymes adding and removing 2-hydroxyisobuty...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2017-08, Vol.114 (33), p.8782-8787
Main Authors: Huang, Jing, Luo, Zhouqing, Ying, Wantao, Cao, Qichen, Huang, He, Dong, Junkai, Wu, Qingyu, Zhao, Yingming, Qian, Xiaohong, Dai, Junbiao
Format: Article
Language:English
Subjects:
Alanine
Biological Sciences
Carbon sources
Fungi
Gluconeogenesis
Gluconeogenesis - physiology
Glucose
Glucose - metabolism
Glycolysis
Glycolysis - physiology
Histone Deacetylases - metabolism
Histones
Histones - metabolism
Homeostasis
Homeostasis - physiology
Life expectancy
Life span
Lysine
Lysine - metabolism
Metabolism
Proteins
Proteomics
Proteomics - methods
Saccharomyces cerevisiae
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - metabolism
Transcription
Transcription, Genetic - physiology
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Summary:New types of modifications of histones keep emerging. Recently, histone H4K8 2-hydroxyisobutyrylation (H4K8hib) was identified as an evolutionarily conserved modification. However, how this modification is regulated within a cell is still elusive, and the enzymes adding and removing 2-hydroxyisobutyrylation have not been found. Here, we report that the amount of H4K8hib fluctuates in response to the availability of carbon source in Saccharomyces cerevisiae and that low-glucose conditions lead to diminished modification. The removal of the 2-hydroxyisobutyryl group from H4K8 is mediated by the histone lysine deacetylase Rpd3p and Hos3p in vivo. In addition, eliminating modifications at this site by alanine substitution alters transcription in carbon transport/metabolism genes and results in a reduced chronological life span (CLS). Furthermore, consistent with the glucose-responsive H4K8hib regulation, proteomic analysis revealed that a large set of proteins involved in glycolysis/gluconeogenesis are modified by lysine 2-hydroxyisobutyrylation. Cumulatively, these results established a functional and regulatory network among Khib, glucose metabolism, and CLS.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1700796114