Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Genome Res. 2010 Jun;20(6):804-15. doi: 10.1101/gr.100594.109. Epub 2010 Mar 10.
Mammalian preimplantation embryonic development (PED) is thought to be governed by highly conserved processes. While it had been suggested that some plasticity of conserved signaling networks exists among different mammalian species, it was not known to what extent modulation of the genomes and the regulatory proteins could "rewire" the gene regulatory networks (GRN) that control PED. We therefore generated global transcriptional profiles from three mammalian species (human, mouse, and bovine) at representative stages of PED, including: zygote, two-cell, four-cell, eight-cell, 16-cell, morula and blastocyst. Coexpression network analysis suggested that 40.2% orthologous gene triplets exhibited different expression patterns among these species. Combining the expression data with genomic sequences and the ChIP-seq data of 16 transcription regulators, we observed two classes of genomic changes that contributed to interspecies expression difference, including single nucleotide mutations leading to turnover of transcription factor binding sites, and insertion of cis-regulatory modules (CRMs) by transposons. About 10% of transposons are estimated to carry CRMs, which may drive species-specific gene expression. The two classes of genomic changes act in concert to drive mouse-specific expression of MTF2, which links POU5F1/NANOG to NOTCH signaling. We reconstructed the transition of the GRN structures as a function of time during PED. A comparison of the GRN transition processes among the three species suggested that in the bovine system, POU5F1's interacting partner SOX2 may be replaced by HMGB1 (a TF sharing the same DNA binding domain with SOX2), resulting in rewiring of GRN by a trans change.
哺乳动物的胚胎着床前发育（PED）被认为是由高度保守的过程控制的。虽然有人提出，不同哺乳动物物种之间的保守信号网络存在一定的可塑性，但对于基因组和调节蛋白的调节在多大程度上可以“重新连接”控制 PED 的基因调控网络（GRN），还不得而知。因此，我们在 PED 的代表阶段（包括：受精卵、二细胞期、四细胞期、八细胞期、十六细胞期、桑椹胚和囊胚），从三个哺乳动物物种（人类、小鼠和牛）中生成了全局转录谱。共表达网络分析表明，40.2%的同源基因三联体在这些物种中表现出不同的表达模式。将表达数据与基因组序列和 16 个转录调节因子的 ChIP-seq 数据相结合，我们观察到两种导致种间表达差异的基因组变化，包括导致转录因子结合位点转换的单核苷酸突变，以及转座子插入顺式调控模块（CRMs）。估计约 10%的转座子携带 CRM，这可能会驱动物种特异性基因表达。这两类基因组变化协同作用，驱动了 MTF2 的小鼠特异性表达，而 MTF2 将 POU5F1/NANOG 与 NOTCH 信号联系起来。我们重建了 PED 过程中 GRN 结构随时间的转变。对三个物种的 GRN 转变过程的比较表明，在牛系统中，POU5F1 的相互作用伙伴 SOX2 可能被 HMGB1（与 SOX2 具有相同 DNA 结合结构域的 TF）取代，从而导致 GRN 通过 Trans 变化重新布线。
