Krishnamoorthy Thanuja, Chen Xin, Govin Jerome, Cheung Wang L, Dorsey Jean, Schindler Karen, Winter Edward, Allis C David, Guacci Vincent, Khochbin Saadi, Fuller Margaret T, Berger Shelley L
Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Genes Dev. 2006 Sep 15;20(18):2580-92. doi: 10.1101/gad.1457006.
Sporulation in Saccharomyces cerevisiae is a highly regulated process wherein a diploid cell gives rise to four haploid gametes. In this study we show that histone H4 Ser1 is phosphorylated (H4 S1ph) during sporulation, starting from mid-sporulation and persisting to germination, and is temporally distinct from earlier meiosis-linked H3 S10ph involved in chromosome condensation. A histone H4 S1A substitution mutant forms aberrant spores and has reduced sporulation efficiency. Deletion of sporulation-specific yeast Sps1, a member of the Ste20 family of kinases, nearly abolishes the sporulation-associated H4 S1ph modification. H4 S1ph may promote chromatin compaction, since deletion of SPS1 increases accessibility to antibody immunoprecipitation; furthermore, either deletion of Sps1 or an H4 S1A substitution results in increased DNA volume in nuclei within spores. We find H4 S1ph present during Drosophila melanogaster and mouse spermatogenesis, and similar to yeast, this modification extends late into sperm differentiation relative to H3 S10ph. Thus, H4 S1ph may be an evolutionarily ancient histone modification to mark the genome for gamete-associated packaging.
酿酒酵母中的孢子形成是一个高度受调控的过程，在此过程中，二倍体细胞会产生四个单倍体配子。在本研究中，我们发现组蛋白H4的丝氨酸1位点在孢子形成过程中会被磷酸化（H4 S1ph），从中期孢子形成开始并持续到萌发，并且在时间上与早期参与染色体浓缩的减数分裂相关的H3 S10ph不同。组蛋白H4 S1A替代突变体形成异常孢子，且孢子形成效率降低。删除孢子形成特异性酵母Sps1（一种Ste20家族激酶成员）几乎消除了与孢子形成相关的H4 S1ph修饰。H4 S1ph可能促进染色质压缩，因为删除SPS1会增加抗体免疫沉淀的可及性；此外，删除Sps1或进行H4 S1A替代都会导致孢子内核中DNA体积增加。我们发现在黑腹果蝇和小鼠精子发生过程中存在H4 S1ph，并且与酵母类似，相对于H3 S10ph，这种修饰在精子分化后期仍持续存在。因此，H4 S1ph可能是一种进化上古老的组蛋白修饰，用于标记与配子相关包装的基因组。
