Transcription in the Absence of Histone H3.2 and H3K4 Methylation
Transcription in the Absence of Histone H3.2 and H3K4 Methylation
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DOI：
10.1016/j.cub.2012.10.008
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发表时间：
2012-12-04
期刊：
影响因子：
9.2
通讯作者：
Basler, Konrad
中科院分区：
文献类型：
--
作者：
Hoedl, Martina;Basler, Konrad
组蛋白H3蛋白在DNA包装、基因转录和表观遗传状态的传递中发挥着重要作用。除了对它们的N末端进行翻译后修饰外，H3变体的使用也有助于它们的调控。典型的组蛋白H3.2在S时相表达，与变异型组蛋白H3.3相差4个氨基酸残基，后者是以不依赖于细胞周期的方式合成的[1]。由于H3.3在活跃的转录位点[1-3]中富含，而且H3赖氨酸4的二甲基化和三甲基化是基因组中这些位置染色质的标志[4]，H3.3K4残基被认为是基因转录状态的主要调控决定因素。在这里，我们使用遗传方法在果蝇中用突变的衍生物替换His3.2的全部46个基因拷贝，从而证明了规范的和变异的H3可以在功能上相互替换。当完全不存在H3.2但被S时相表达的H3.3取代时，细胞能够分裂和分化。此外，尽管细胞的增殖能力减慢，但在所有规范和变异的H3基因中编码非甲基化残基而不是K4的细胞有能力通过激活靶基因表达来响应主要的发育信号通路。因此，在果蝇中，不同的H3蛋白种类的存在并不是必需的，在完全没有H3K4甲基化的情况下，转录调节可以发生。
Histone H3 proteins play fundamental roles in DNA packaging, gene transcription, and the transmission of epigenetic states. In addition to posttranslational modifications of their N termini, the use of H3 variants contributes to their regulatory repertoire. Canonical histone H3.2 is expressed during S phase and differs by four amino acid residues from the variant histone H3.3, which is synthesized in a cell-cycle-independent manner [1]. Because H3.3 is enriched within actively transcribed loci [1-3], and because di- and trimethylation of H3 lysine 4 are hallmarks of chromatin at such sites in the genome [4], the H3.3K4 residue is considered to serve as the major regulatory determinant for the transcriptional state of a gene. Here we use genetic approaches in Drosophila to replace all 46 gene copies of His3.2 with mutant derivatives and thereby demonstrate that canonical and variant H3 can functionally replace each other. Cells are able to divide and differentiate when H3.2 is entirely absent but replaced by S phase-expressed H3.3. Moreover, although slowed down in their proliferative capacity, cells that code for a nonmethylatable residue instead of K4 in all canonical and variant H3 genes are competent to respond to major developmental signaling pathways by activating target gene expression. Hence, the presence of different H3 protein species is not essential in Drosophila and transcriptional regulation can occur in the complete absence of H3K4 methylation.