Post‐translational modifications of histones: Mechanisms, biological functions, and therapeutic targets

Abstract

Histones are DNA‐binding basic proteins found in chromosomes. After the histone translation, its amino tail undergoes various modifications, such as methylation, acetylation, phosphorylation, ubiquitination, malonylation, propionylation, butyrylation, crotonylation, and lactylation, which together constitute the “histone code.” The relationship between their combination and biological function can be used as an important epigenetic marker. Methylation and demethylation of the same histone residue, acetylation and deacetylation, phosphorylation and dephosphorylation, and even methylation and acetylation between different histone residues cooperate or antagonize with each other, forming a complex network. Histone‐modifying enzymes, which cause numerous histone codes, have become a hot topic in the research on cancer therapeutic targets. Therefore, a thorough understanding of the role of histone post‐translational modifications (PTMs) in cell life activities is very important for preventing and treating human diseases. In this review, several most thoroughly studied and newly discovered histone PTMs are introduced. Furthermore, we focus on the histone‐modifying enzymes with carcinogenic potential, their abnormal modification sites in various tumors, and multiple essential molecular regulation mechanism. Finally, we summarize the missing areas of the current research and point out the direction of future research. We hope to provide a comprehensive understanding and promote further research in this field.

Epigenetic Regulation of Autophagy in Bone Metabolism

“…Histone acetyltransferases facilitate the attachment of acetyl-CoA molecules onto histones, promoting a relaxed nucleosome structure. 43 This structural change activates the transcriptional machinery, enhancing gene expression. In cases where HAT activity is hindered or inhibited, the repair of damaged DNA may be compromised, potentially resulting in cellular apoptosis or programmed cell death.…”

Autoimmune Disorders Unraveled: The Interplay Between Genetics and the Immune System.

“…These changes may affect the activation or suppression of certain immunoregulatory genes. Dysregulated histone modifications have been linked to differentiation of immune cells, cytokine production and inflammatory response in autoimmune diseases (36) .…”

Epigenetics in myeloproliferative neoplasms

“…These modifications primarily include acetylation, methylation, and phosphorylation. Other histone posttranslational modifications including butyrylation and sumoylation ( 4 ) are increasingly recognized, but their relevance in MPN is unclear and they will not be discussed in this review.…”

“…HDACs can be divided into three classes. Class I HDACs (1, 2, 3, and 8) are located in the nucleus, Class II HDACs ( 4 – 9 ) are located in the nucleus and cytoplasm, and Class III HDACs are distinct NAD-dependent enzymes ( 6 ). Class I and II HDACs are inhibited by suberoylanilide hydroxamic acid (SAHA) and other HDAC inhibitors inducing growth arrest, differentiation, apoptosis, and inhibition of tumor growth in cancers including hematological malignancy ( 7 ).…”