INSERM, U823, Institut Albert Bonniot, Université Joseph Fourier - Grenoble 1, Grenoble, France.
Andrology. 2014 May;2(3):351-9. doi: 10.1111/j.2047-2927.2014.00184.x. Epub 2014 Feb 13.
Histone hyperacetylation is thought to drive the replacement of histones by transition proteins that occur in elongating spermatids (ElS) after a general shut down of transcription. The molecular machineries underlying this histone hyperacetylation remain still undefined. Here, we focused our attention on the role of Cbp and p300 in histone hyperacetylation and in the preceding late-gene transcriptional activity in ElS. A strategy was designed to partially deplete Cbp and p300 in ElS. These cells progressed normally through spermiogenesis and showed normal histone hyperacetylation and removal. However, a genome-wide transcriptomic analysis, performed in the round spermatids (RS) and ElS, revealed the existence of a gene regulatory circuit encompassing genes presenting high expression levels in pre-meiotic cells, undergoing a repressed state in spermatocytes and early post-meiotic cells, but becoming reactivated in ElS, just prior to the global shutdown of transcription. Interestingly, this group of genes was over-represented within the genes affected by Cbp/p300 knock down and were all involved in metabolic remodelling. This study revealed the occurrence of a tightly regulated Cbp/p300-dependent gene expression programme that drives a specific metabolic state both in progenitor spermatogenic cells and in late transcriptionally active spermatids and confirmed a special link between Cpb/p300 and cell metabolism programming previously shown in somatic cells.
组蛋白乙酰化被认为驱动了转换蛋白取代组蛋白，这种取代发生在转录普遍关闭之后的伸长精子细胞（ElS）中。支持这种组蛋白超乙酰化的分子机制仍然不清楚。在这里，我们将注意力集中在 Cbp 和 p300 在 ElS 中的组蛋白超乙酰化和先前的晚期基因转录活性中的作用。设计了一种策略来部分耗尽 ElS 中的 Cbp 和 p300。这些细胞正常地通过精子发生过程，表现出正常的组蛋白超乙酰化和去除。然而，在圆形精子细胞（RS）和 ElS 中进行的全基因组转录组分析揭示了一个基因调控回路的存在，该回路包含在减数前期细胞中高表达水平的基因，在精母细胞和早期减数后细胞中处于抑制状态，但在 ElS 中重新激活，就在转录全面关闭之前。有趣的是，这群基因在受 Cbp/p300 敲低影响的基因中过度表达，并且都与代谢重编程有关。这项研究揭示了一个严格调控的 Cbp/p300 依赖性基因表达程序的发生，该程序在祖细胞生殖细胞和晚期转录活跃的精子细胞中驱动了一种特定的代谢状态，并证实了 Cpb/p300 与细胞代谢编程之间以前在体细胞中显示的特殊联系。
