EMBL-CRG Systems Biology Unit, Centre for Genomic Regulation, Universitat Pompeu Fabra, Barcelona, Spain.
PLoS Genet. 2011 Apr;7(4):e1002036. doi: 10.1371/journal.pgen.1002036. Epub 2011 Apr 7.
Chromatin in sperm is different from that in other cells, with most of the genome packaged by protamines not nucleosomes. Nucleosomes are, however, retained at some genomic sites, where they have the potential to transmit paternal epigenetic information. It is not understood how this retention is specified. Here we show that base composition is the major determinant of nucleosome retention in human sperm, predicting retention very well in both genic and non-genic regions of the genome. The retention of nucleosomes at GC-rich sequences with high intrinsic nucleosome affinity accounts for the previously reported retention at transcription start sites and at genes that regulate development. It also means that nucleosomes are retained at the start sites of most housekeeping genes. We also report a striking link between the retention of nucleosomes in sperm and the establishment of DNA methylation-free regions in the early embryo. Taken together, this suggests that paternal nucleosome transmission may facilitate robust gene regulation in the early embryo. We propose that chromatin organization in the male germline, rather than in somatic cells, is the major functional consequence of fine-scale base composition variation in the human genome. The selective pressure driving base composition evolution in mammals could, therefore, be the need to transmit paternal epigenetic information to the zygote.
精子中的染色质不同于其他细胞中的染色质，大多数基因组被鱼精蛋白而非核小体包裹。然而，核小体在一些基因组位点被保留下来，这些位点有可能传递父系表观遗传信息。目前尚不清楚这种保留是如何被指定的。在这里，我们表明碱基组成是人类精子中核小体保留的主要决定因素，它可以很好地预测基因组中基因和非基因区域的核小体保留。富含 GC 的序列具有较高的固有核小体亲和力，这解释了之前报道的转录起始位点和调控发育的基因的核小体保留。这也意味着核小体保留在大多数管家基因的起始位点。我们还报告了精子中核小体保留与早期胚胎中 DNA 去甲基化区域建立之间的惊人联系。综上所述，这表明父系核小体传递可能有助于早期胚胎中基因的稳健调控。我们提出，在雄性生殖细胞中而不是在体细胞中，染色质组织是人类基因组中碱基组成精细变化的主要功能后果。驱动哺乳动物碱基组成进化的选择压力可能是需要将父系表观遗传信息传递给受精卵。
