Eukaryotes package their DNA into chromatin with histones. An ever-growing number of histone post-translational modifications have been discovered, which facilitate and modulate chromatin-based fundamental processes, such as transcription, DNA damage repair, and DNA replication. Lysine residues are the most modified histone residues. Acetylation and methylation on lysine residues are the two most studied histone modifications, and they differ greatly in one biophysical property. Acetylation neutralizes the positive charges on lysine residues and attenuates the interaction between positively charged histone tails and negatively charged DNA. This endows lysine acetylation per se an important function, chromatin decompaction. However, lysine methylation does not alter the charges carried by histones and its function relies on associated reader proteins to translate site-specific lysine methylation into epigenetic information that executes downstream cellular programs. To date, readers of almost all major histone methylation marks have been identified except for histone H3 lysine 79 (H3K79) methylation [1]. DOT1L, a conserved protein from yeast to humans, is the sole methyltransferase responsible for H3K79 methylation [2]. H3K79 methylation is typically enriched at active genes and its function has been implicated in transcription, DNA damage response, and cell cycle regulation [3]. Moreover, aberrant H3K79 methylation is often observed in MLL-rearranged (MLL-r) leukemia [4]. Despite the important role of DOT1L in cellular and developmental processes and diseases, our understanding of the downstream effects of DOT1L-catalyzed H3K79 methylation is still limited because the reader(s) of H3K79 methylation has not been unveiled. Recently, using a nucleosome-based photoaffinity probe, Lin et al. [5] identified menin, a subunit of the MLL1/2 COMPASS-like complexes, as a bona fide reader of di-methylated H3K79 (H3K79me2).
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Menin, the COMPASS to locate H3K79 dimethylation,Sci Bull, 25 Feb 2023
Science Bulletin, 25 February, 2023, DOI：https://doi.org/10.1016/j.scib.2023.02.033
Menin, the COMPASS to locate H3K79 dimethylation
Qinchao Zhou, Jun Xiong, Bing Zhu
Abstract
Eukaryotes package their DNA into chromatin with histones. An ever-growing number of histone post-translational modifications have been discovered, which facilitate and modulate chromatin-based fundamental processes, such as transcription, DNA damage repair, and DNA replication. Lysine residues are the most modified histone residues. Acetylation and methylation on lysine residues are the two most studied histone modifications, and they differ greatly in one biophysical property. Acetylation neutralizes the positive charges on lysine residues and attenuates the interaction between positively charged histone tails and negatively charged DNA. This endows lysine acetylation per se an important function, chromatin decompaction. However, lysine methylation does not alter the charges carried by histones and its function relies on associated reader proteins to translate site-specific lysine methylation into epigenetic information that executes downstream cellular programs. To date, readers of almost all major histone methylation marks have been identified except for histone H3 lysine 79 (H3K79) methylation [1]. DOT1L, a conserved protein from yeast to humans, is the sole methyltransferase responsible for H3K79 methylation [2]. H3K79 methylation is typically enriched at active genes and its function has been implicated in transcription, DNA damage response, and cell cycle regulation [3]. Moreover, aberrant H3K79 methylation is often observed in MLL-rearranged (MLL-r) leukemia [4]. Despite the important role of DOT1L in cellular and developmental processes and diseases, our understanding of the downstream effects of DOT1L-catalyzed H3K79 methylation is still limited because the reader(s) of H3K79 methylation has not been unveiled. Recently, using a nucleosome-based photoaffinity probe, Lin et al. [5] identified menin, a subunit of the MLL1/2 COMPASS-like complexes, as a bona fide reader of di-methylated H3K79 (H3K79me2).
文章链接：https://www.sciencedirect.com/science/article/pii/S2095927323001378?via%3Dihub