A review of: Lysine-79 of histone H3 is hypomethylated at silenced loci in yeast and mammalian cells: a potential mechanism for position-effect variegation. Ng HH, Ciccone DN, Morshead KB, Oettinger MA, Struhl K. Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1820-5. doi: 10.1073/pnas.0437846100.
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DNA is the blueprint of life, making the roles that histones and their modifications play exceptionally important. Modifications in histone tail and globular domains, like methylation and acetylation, are essential for determining chromatin structure and transcription among other functions. In 2003, Ng and colleagues published a paper that was crucial in progressing the field of epigenetics. It explored the role of Dot1-mediated H3- lysine 79 methylation in the regulation of heterochromatin formation at silenced loci and helped pave the way for epigenetics as it’s known today. Ng and his colleagues discovered that H3-K79 is methylated in recombinationally active regions, but essentially unmethylated at inert regions respectively. The research performed by Ng and his colleagues helped to elucidate the role of Dot1 and H3-K79 methylation in heterochromatin formation, advancing our understanding of transcriptional repression. We are only just starting to understand the importance and far-reaching implications of epigenetic modifications, such as the methylation of H3-K79 explored by Ng and his colleagues. Subsequent research has established that the Dot1 mammalian homolog, DOT1L, plays a key role in many processes including embryogenesis, cell cycle regulation and DNA damage repair, and the pathogenesis of leukemia. Hence, the research conducted by Ng and his colleagues not only contributed an invaluable piece to the epigenetic puzzle, but also laid the foundation for countless breakthroughs in biology and medicine.
Creator: MD Hobson
References:
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Ng H. H., D. N. Ciccone, K. B. Morshead, M. A. Oettinger, K. Struhl, 2003 Lysine-79 of histone H3 is hypomethylated at silenced loci in yeast and mammalian cells: A potential mechanism for position-effect variegation. Proceedings of the National Academy of Sciences 100: 1820-1825.
Ng H. H., Q. Feng, H. Wang, H. Erdjument-Bromage, P. Tempst, Y. Zhang, K. Struhl, 2002 Lysine methylation within the globular domain of histone H3 by Dot1 is important for telomeric silencing and Sir protein association. Genes & Development 16: 1518-1527.
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Zhang T., S. Cooper, N. Brockdorff, 2015 The interplay of histone modifications – writers that read. EMBO reports 16: 1467-1481.
