Department of Urology, Pediatric Urology and Andrology, Justus Liebig University of Giessen, Giessen, Germany.
Epigenetics. 2012 Sep;7(9):1057-70. doi: 10.4161/epi.21556. Epub 2012 Aug 16.
Sperm chromatin reveals two characteristic features in that protamines are the predominant nuclear proteins and remaining histones are highly acetylated. Histone H4 acetylated at lysine 12 (H4K12ac) is localized in the post-acrosomal region, while protamine-1 is present within the whole nucleus. Chromatin immunoprecipitation in combination with promoter array analysis allowed genome-wide identification of H4K12ac binding sites. Previously, we reported enrichment of H4K12ac at CTCF binding sites and promoters of genes involved in developmental processes. Here, we demonstrate that H4K12ac is enriched predominantly between ± 2 kb from the transcription start site. In addition, we identified developmentally relevant H4K12ac-associated promoters with high expression levels of their transcripts stored in mature sperm. The highest expressed mRNA codes for testis-specific PHD finger protein-7 (PHF7), suggesting an activating role of H4K12ac in the regulatory elements of this gene. H4K12ac-associated genes revealed a weak correlation with genes expressed at 4-cell stage human embryos, while 23 H4K12ac-associated genes were activated in 8-cell embryo and 39 in the blastocyst. Genes activated in 4-cell embryos are involved in gene expression, histone fold and DNA-dependent transcription, while genes expressed in the blastocyst were classified as involved in developmental processes. Immunofluorescence staining detected H4K12ac from the murine male pronucleus to early stages of embryogenesis. Aberrant histone acetylation within developmentally important gene promoters in infertile men may reflect insufficient sperm chromatin compaction, which may result in inappropriate transfer of epigenetic information to the oocyte.
精子染色质具有两个特征性特征，即鱼精蛋白是主要的核蛋白，而剩余的组蛋白高度乙酰化。赖氨酸 12 乙酰化的组蛋白 H4（H4K12ac）定位于顶体后区，而鱼精蛋白-1存在于整个核内。染色质免疫沉淀与启动子阵列分析相结合，允许对 H4K12ac 结合位点进行全基因组鉴定。以前，我们报道了 H4K12ac 在 CTCF 结合位点和参与发育过程的基因启动子处的富集。在这里，我们证明 H4K12ac 主要富集在转录起始位点的±2kb 范围内。此外，我们鉴定了与发育相关的 H4K12ac 相关启动子，其转录本的表达水平较高，储存在成熟精子中。表达水平最高的 mRNA 编码睾丸特异性 PHF7 结构域蛋白-7（PHF7），这表明 H4K12ac 在该基因的调节元件中具有激活作用。H4K12ac 相关基因与在 4 细胞期人类胚胎中表达的基因呈弱相关，而 23 个 H4K12ac 相关基因在 8 细胞胚胎中激活，39 个在囊胚中激活。在 4 细胞胚胎中激活的基因参与基因表达、组蛋白折叠和 DNA 依赖性转录，而在囊胚中表达的基因被归类为参与发育过程。免疫荧光染色检测到来自雄性小鼠原核的 H4K12ac 到早期胚胎发生阶段。在不育男性中，发育重要基因启动子中异常的组蛋白乙酰化可能反映了精子染色质紧缩不足，这可能导致表观遗传信息向卵母细胞的不当传递。
