Tsusaka Takeshi, Oses-Prieto Juan A, Lee Christina, DeFelice Brian C, Burlingame Alma L, Goldberg Emily L
Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA.
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
iScience. 2023 Jun 29;26(7):107235. doi: 10.1016/j.isci.2023.107235. eCollection 2023 Jul 21.
Ketone bodies are short-chain fatty acids produced in the liver during periods of limited glucose availability that provide an alternative energy source for the brain, heart, and skeletal muscle. Beyond this metabolic role, β-hydroxybutyrate (BHB), is gaining recognition as a signaling molecule. Lysine β-hydroxybutyrylation (Kbhb) is a newly discovered post-translational modification in which BHB is covalently attached to lysine ε-amino groups. This protein adduct is metabolically sensitive, dependent on BHB concentration, and found on proteins in multiple intracellular compartments. Therefore, Kbhb is hypothesized to be an important component of ketone body-regulated physiology. Kbhb on histones is proposed to be an epigenetic regulator, which links metabolic alterations to gene expression. However, we found that the widely used antibody against β-hydroxybutyrylated lysine 9 on histone H3 (H3K9bhb) also recognizes other modification(s) that likely include acetylation. Therefore, caution must be used when interpreting gene regulation data acquired with the H3K9bhb antibody.
酮体是在葡萄糖供应有限的时期于肝脏中产生的短链脂肪酸，为大脑、心脏和骨骼肌提供了一种替代能源。除了这种代谢作用外，β-羟基丁酸酯（BHB）正逐渐被认可为一种信号分子。赖氨酸β-羟基丁酰化（Kbhb）是一种新发现的翻译后修饰，其中BHB共价连接到赖氨酸的ε-氨基上。这种蛋白质加合物对代谢敏感，依赖于BHB浓度，并且存在于多个细胞内区室的蛋白质上。因此，推测Kbhb是酮体调节生理学的一个重要组成部分。组蛋白上的Kbhb被认为是一种表观遗传调节剂，它将代谢改变与基因表达联系起来。然而，我们发现广泛使用的抗组蛋白H3上β-羟基丁酰化赖氨酸9（H3K9bhb）的抗体也识别其他可能包括乙酰化的修饰。因此，在用H3K9bhb抗体获取基因调控数据时必须谨慎解读。
