Department of Biology, University of Rome 'Tor Vergata', Via Della Ricerca Scientifica 1, 00133, Rome, Italy.
Department of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases IRCCS 'L. Spallanzani', Rome, Italy.
Cell Mol Life Sci. 2023 Jan 25;80(2):52. doi: 10.1007/s00018-023-04698-8.
One of the major mysteries in science is how it is possible to pack the cellular chromatin with a total length of over 1 m, into a small sphere with a diameter of 5 mm "the nucleus", and even more difficult to envisage how to make it functional. Although we know that compaction is achieved through the histones, however, the DNA needs to be accessible to the transcription machinery and this is allowed thanks to a variety of very complex epigenetic mechanisms. Either DNA (methylation) or post-translational modifications of histone proteins (acetylation, methylation, ubiquitination and sumoylation) play a crucial role in chromatin remodelling and consequently on gene expression. Recently the serotonylation and dopaminylation of the histone 3, catalyzed by the Transglutaminase type 2 (TG2), has been reported. These novel post-translational modifications catalyzed by a predominantly cytoplasmic enzyme opens a new avenue for future investigations on the enzyme function itself and for the possibility that other biological amines, substrate of TG2, can influence the genome regulation under peculiar cellular conditions. In this review we analyzed the nuclear TG2's biology by discussing both its post-translational modification of various transcription factors and the implications of its epigenetic new face. Finally, we will focus on the potential impact of these events in human diseases.
科学中的一个主要谜团是，如何将总长超过 1 米的细胞染色质包装到直径为 5 毫米的“细胞核”中，更难以想象的是如何使其具有功能性。尽管我们知道通过组蛋白实现了压缩，但 DNA 需要能够被转录机制访问，这得益于各种非常复杂的表观遗传机制。无论是 DNA（甲基化）还是组蛋白蛋白质的翻译后修饰（乙酰化、甲基化、泛素化和 sumoylation），在染色质重塑和基因表达中都起着至关重要的作用。最近，组蛋白 3 的 Serotonylation 和 Dopaminylation 已被报道，由 Transglutaminase type 2（TG2）催化。这种由主要位于细胞质中的酶催化的新型翻译后修饰为未来研究该酶的功能本身以及其他生物胺（TG2 的底物）是否可以在特定的细胞条件下影响基因组调控开辟了新途径。在这篇综述中，我们通过讨论 TG2 对各种转录因子的翻译后修饰及其表观遗传新面孔的影响，分析了核 TG2 的生物学。最后，我们将重点关注这些事件在人类疾病中的潜在影响。
