Howard Hughes Medical Institute, Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.
Genome Res. 2011 Apr;21(4):578-89. doi: 10.1101/gr.113167.110. Epub 2011 Mar 7.
In mature human sperm, genes of importance for embryo development (i.e., transcription factors) lack DNA methylation and bear nucleosomes with distinctive histone modifications, suggesting the specialized packaging of these developmental genes in the germline. Here, we explored the tractable zebrafish model and found conceptual conservation as well as several new features. Biochemical and mass spectrometric approaches reveal the zebrafish sperm genome packaged in nucleosomes and histone variants (and not protamine), and we find linker histones high and H4K16ac absent, key factors that may contribute to genome condensation. We examined several activating (H3K4me2/3, H3K14ac, H2AFV) and repressing (H3K27me3, H3K36me3, H3K9me3, hypoacetylation) modifications/compositions genome-wide and find developmental genes packaged in large blocks of chromatin with coincident activating and repressing marks and DNA hypomethylation, revealing complex "multivalent" chromatin. Notably, genes that acquire DNA methylation in the soma (muscle) are enriched in transcription factors for alternative cell fates. Remarkably, whereas H3K36me3 is located in the 3' coding region of heavily transcribed genes in somatic cells, H3K36me3 is present in the promoters of "silent" developmental regulators in sperm, suggesting different rules for H3K36me3 in the germline and soma. We also reveal the chromatin patterns of transposons, rDNA, and tDNAs. Finally, high levels of H3K4me3 and H3K14ac in sperm are correlated with genes activated in embryos prior to the mid-blastula transition (MBT), whereas multivalent genes are correlated with activation at or after MBT. Taken together, gene sets with particular functions in the embryo are packaged by distinctive types of complex and often atypical chromatin in sperm.
在成熟的人类精子中，对胚胎发育重要的基因（即转录因子）缺乏 DNA 甲基化，并带有具有独特组蛋白修饰的核小体，这表明这些发育基因在生殖细胞中被专门包装。在这里，我们探索了易于处理的斑马鱼模型，发现了概念上的保守性以及一些新特征。生化和质谱方法揭示了斑马鱼精子基因组被包装在核小体和组蛋白变体（而不是鱼精蛋白）中，并且我们发现连接组蛋白含量高，H4K16ac 不存在，这是可能有助于基因组浓缩的关键因素。我们检查了几种激活（H3K4me2/3、H3K14ac、H2AFV）和抑制（H3K27me3、H3K36me3、H3K9me3、低乙酰化）修饰/组成的全基因组，并发现发育基因被包装在具有协同激活和抑制标记以及 DNA 低甲基化的大染色质块中，揭示了复杂的“多价”染色质。值得注意的是，在体细胞中获得 DNA 甲基化的基因在用于替代细胞命运的转录因子中富集。值得注意的是，虽然 H3K36me3 位于体细胞中高度转录基因的 3'编码区，但 H3K36me3 存在于精子中“沉默”发育调节剂的启动子中，这表明 H3K36me3 在生殖细胞和体细胞中的规则不同。我们还揭示了转座子、rDNA 和 tDNA 的染色质模式。最后，精子中 H3K4me3 和 H3K14ac 的高水平与中胚层转变（MBT）之前胚胎中激活的基因相关，而多价基因与 MBT 前后的激活相关。总之，在胚胎中具有特定功能的基因集被独特类型的复杂且通常非典型的染色质包装。
