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The epigenetic magic of histone lysine methylation

机译：组蛋白赖氨酸甲基化的表观遗传学魔术

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摘要

Epigenetic mechanisms control eukaryotic development beyond DNA-stored information. There are several pathways, including histone tail modifications, histone variant incorporation, nucleosome remodelling, DNA methylation and noncoding RNAs that together all contribute to the dynamic 'make-up' of chromatin under distinct developmental options. The histone tail modifications are most variable and over 50 marks have by now been mapped. While the majority of these modifications are transient, histone lysine methylation and, in particular, a histone lysine tri-methyl state has been regarded as a more robust signal, consistent with proposed roles to impart long-term epigenetic memory. Based on the paradigm of SET-domain histone lysine methyltransferases (HMTases) and chromo-domain adaptor proteins, and in conjunction with the Sir Hans Krebs Medal 2005, I describe here my personal view on the discovery of the first HMTase in 2000, and the subsequent advances on the biology of histone lysine methylation. This discovery has changed my scientific career and significantly contributed to a better understanding of epigenetic control, with important implications for heterochromatin formation, X inactivation, Polycomb group silencing and novel insights into stem cell research, nuclear reprogramming and cancer.
机译：表观遗传机制控制着真核生物的发展，超越了DNA储存的信息。存在多种途径，包括组蛋白尾部修饰，组蛋白变体掺入，核小体重塑，DNA甲基化和非编码RNA，这些途径在不同的发育选择下共同促进了染色质的动态“合成”。组蛋白尾部修饰的变化最大，到目前为止已绘制了50多个标记。尽管这些修饰大多数是瞬时的，但组蛋白赖氨酸甲基化，尤其是组蛋白赖氨酸三甲基状态被认为是更可靠的信号，与赋予长期表观遗传记忆的拟议作用一致。基于SET域组蛋白赖氨酸甲基转移酶（HMTases）和染色体域衔接蛋白的范例，并结合2005年Hans Krebs勋章，我对2000年发现首个HMTase以及组蛋白赖氨酸甲基化的生物学进展。这一发现改变了我的科学生涯，并极大地促进了对表观遗传控制的更好理解，对异染色质形成，X失活，Polycomb组沉默以及对干细胞研究，核重编程和癌症的新颖见解具有重要意义。

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