Rewirable gene regulatory networks in the preimplantation embryonic development of three mammalian species

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Blastocyst*
  • Cattle
  • DNA
  • DNA Transposable Elements
  • Embryonic Development*
  • Gene Regulatory Networks*
  • Humans
  • Mice
  • Molecular Sequence Data
  • Point Mutation
  • Sequence Homology, Nucleic Acid
  • Species Specificity


  • DNA Transposable Elements
  • DNA