β-hydroxybutyrylation-Specific Antibody Production Services

Based on the excellent High-Affi™ technology, Creative Biolabs has the capability of providing highly specific pan anti-β-hydroxybutyryllysine antibody and site-specific anti-β-hydroxybutyrylated protein antibodies production services. These antibodies are produced by optimized immunization with β-hydroxybutyrylated BSA or KLH or with a synthetic β-hydroxybutyryl peptide and purified by affinity chromatography. The pan anti-β-hydroxybutyryllysine antibody specifically recognizes proteins with β-hydroxybutyrylated lysine residues without species limitation, and site-specific anti-β-hydroxybutyrylated antibodies recognize site-specific β-hydroxybutyrylated peptide. They do not cross-react with non-modified lysine residues, unmodified peptides, 2-hydroxyisobutyrylated peptides and acetylated peptides.

Lysine β-hydroxybutyrylation (Kbhb) is a new identified histone post-translational modification in 2016 which is enriched in active gene promoters. It has been found to modify on many lysine residues of all four types of histones (H1, H2A, H2B, H3, H4).

Regulated by β-hydroxybutyrate
Histone lysine β-hydroxybutyrylation was dramatically induced when the level of β-hydroxybutyrate was increased in cultured cells. In addition, when mice were subjected to prolonged fasting or treated with streptozotocin-induced diabetic ketoacidosis, the level of histone Kbhb was elevated. In contrast, histone lysine acetylation (Kac) was only marginal increased. Therefore, β-hydroxybutyrate has a much more profound impact on histone Hbhb than on histone Kac.

Function of histone lysine β-hydroxybutyrylation
When cells suffer starvation, the metabolic pathway is changed from carbohydrate metabolism to fatty acid metabolism. When prolonged fasting, ketone body-derived histone Kbhb is associated with amino acid catabolism. A series of research show that histone Kbhb is enriched in active gene promoters in starvation conditions, and increasing H3K9bhb levels are associated with genes upregulated in starvation-responsive metabolic pathways. Therefore, histone lysine β-hydroxybutyrylation represents a new epigenetic mechanism that couples metabolism to gene expression.

Differential regulation of histone Kbhb and Kac
Proteomic analysis showed that the set of genes upregulated by lysine β-hydroxybutyrylation were distinguished from that of bearing acetylation and methylation, suggesting histone Khbh has different functions from Kac and Kme. It is believed that histone lysine β-hydroxybutyrylation provides a new challenge to maintain physiological homeostasis.

Diseases associated with lysine β-hydroxybutyrylation
Previous work reveals that a ketogenic diet inhibits tumor growth both in animal models and potentially in human patients. It can be speculated that the elevated histone Kbhb levels by ketogenic diet may play a role in the expression of the tumor-suppressive gene. As Kbhb is regulated by metabolism, it may also involve in other human pathophysiological states, such as diabetes.

Histone Kbhb marks are dramatically induced in response to elevated β-hydroxybutyrate levels in cultured cells and livers from mice subjected to prolonged fasting. Histone Kbhb is a mark enriched in active gene promoters during starvation and associated with genes upregulated in starvation-responsive metabolic pathways. Fig. 1. Metabolic regulation of gene expression by histone lysine β-hydroxybutyrylation. (Xie Z, et al. 2016)

However, the diverse effects of β-hydroxybutyrylation remain unclear. More work should be done to uncover the physiological functions of β-hydroxybutyrylation. Antibodies are the most common tools in PTM discovery, sites identification and functional study. Creative Biolabs can provide the global customers with the most comprehensive antibodies discovery and production services, especially in the field of PTM. The products are supplied with high affinity and 100% quality assurance.

Creative Biolabs can provide a comprehensive list of PTM-specific antibody production services of your choice.

Reference

Xie Z, Zhang D, Chung D, et al. (2016) “Metabolic regulation of gene expression by histone lysine beta-hydroxybutyrylation”. Mol Cell, 62(2): 194-206.

All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

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