Ben May Department of Cancer Research, The University of Chicago, Chicago, IL 60637, USA.
Cell. 2011 Sep 16;146(6):1016-28. doi: 10.1016/j.cell.2011.08.008.
We report the identification of 67 previously undescribed histone modifications, increasing the current number of known histone marks by about 70%. We further investigated one of the marks, lysine crotonylation (Kcr), confirming that it represents an evolutionarily-conserved histone posttranslational modification. The unique structure and genomic localization of histone Kcr suggest that it is mechanistically and functionally different from histone lysine acetylation (Kac). Specifically, in both human somatic and mouse male germ cell genomes, histone Kcr marks either active promoters or potential enhancers. In male germinal cells immediately following meiosis, Kcr is enriched on sex chromosomes and specifically marks testis-specific genes, including a significant proportion of X-linked genes that escape sex chromosome inactivation in haploid cells. These results therefore dramatically extend the repertoire of histone PTM sites and designate Kcr as a specific mark of active sex chromosome-linked genes in postmeiotic male germ cells.
我们鉴定了 67 种以前未被描述的组蛋白修饰,将已知的组蛋白标记数量增加了约 70%。我们进一步研究了其中一种标记,赖氨酸巴豆酰化(Kcr),证实它代表了一种进化上保守的组蛋白翻译后修饰。组蛋白 Kcr 的独特结构和基因组定位表明,它在机制和功能上不同于组蛋白赖氨酸乙酰化(Kac)。具体来说,在人类体细胞和小鼠雄性生殖细胞基因组中,组蛋白 Kcr 标记要么是活跃的启动子,要么是潜在的增强子。在减数分裂后立即的雄性生殖细胞中,Kcr 在性染色体上富集,并特异性地标记睾丸特异性基因,包括大量逃避单倍体细胞中性染色体失活的 X 连锁基因。这些结果因此极大地扩展了组蛋白 PTM 位点的范围,并将 Kcr 指定为减数分裂后雄性生殖细胞中活性性染色体连锁基因的特异性标记。