Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States.
Elife. 2023 Oct 3;12:e83952. doi: 10.7554/eLife.83952.
After fertilization, maternally contributed factors to the egg initiate the transition to pluripotency to give rise to embryonic stem cells, in large part by activating de novo transcription from the embryonic genome. Diverse mechanisms coordinate this transition across animals, suggesting that pervasive regulatory remodeling has shaped the earliest stages of development. Here, we show that maternal homologs of mammalian pluripotency reprogramming factors OCT4 and SOX2 divergently activate the two subgenomes of , an allotetraploid that arose from hybridization of two diploid species ~18 million years ago. Although most genes have been retained as two homeologous copies, we find that a majority of them undergo asymmetric activation in the early embryo. Chromatin accessibility profiling and CUT&RUN for modified histones and transcription factor binding reveal extensive differences in predicted enhancer architecture between the subgenomes, which likely arose through genomic disruptions as a consequence of allotetraploidy. However, comparison with diploid and zebrafish shows broad conservation of embryonic gene expression levels when divergent homeolog contributions are combined, implying strong selection to maintain dosage in the core vertebrate pluripotency transcriptional program, amid genomic instability following hybridization.
受精后，卵母细胞中的母体因子启动向多能性的转变，从而产生胚胎干细胞，这在很大程度上是通过从头激活胚胎基因组的转录来实现的。不同的机制在动物之间协调了这一转变，这表明普遍的调控重塑塑造了发育的最早阶段。在这里，我们表明，哺乳动物多能性重编程因子 OCT4 和 SOX2 的母体同源物在杂种起源约 1800 万年前的两个二倍体物种杂交产生的 allotetraploid 中，以不同的方式激活两个亚基因组。尽管大多数基因作为两个同源拷贝被保留下来，但我们发现它们中的大多数在早期胚胎中经历不对称激活。染色质可及性分析和用于修饰组蛋白和转录因子结合的 CUT&RUN 揭示了亚基因组之间预测的增强子结构的广泛差异，这可能是由于 allotetraploidy 导致基因组破坏而产生的。然而，与二倍体 和斑马鱼的比较表明，当不同的同源物贡献结合在一起时，胚胎基因表达水平广泛保守，这意味着在杂交后基因组不稳定的情况下，在核心脊椎动物多能性转录程序中维持剂量的强烈选择。
