Examination of transcriptional networks reveals an important role for TCFAP2C, SMARCA4, and EOMES in trophoblast stem cell maintenance

Genome Res. 2010 Apr;20(4):458-72. doi: 10.1101/gr.101469.109. Epub 2010 Feb 22.


Trophoblast stem cells (TS cells), derived from the trophectoderm (TE) of blastocysts, require transcription factors (TFs) and external signals (FGF4, INHBA/NODAL/TGFB1) for self-renewal. While many reports have focused on TF networks that regulate embryonic stem cell (ES cell) self-renewal and pluripotency, little is know about TF networks that regulate self-renewal in TS cells. To further understand transcriptional networks in TS cells, we used chromatin immunoprecipitation with DNA microarray hybridization (ChIP-chip) analysis to investigate targets of the TFs-TCFAP2C, EOMES, ETS2, and GATA3-and a chromatin remodeling factor, SMARCA4. We then evaluated the transcriptional states of target genes using transcriptome analysis and genome-wide analysis of histone H3 acetylation (AcH3). Our results describe previously unknown transcriptional networks in TS cells, including TF occupancy of genes involved in ES cell self-renewal and pluripotency, co-occupancy of TCFAP2C, SMARCA4, and EOMES at a significant number of genes, and transcriptional regulatory circuitry within the five factors. Moreover, RNAi depletion of Tcfap2c, Smarca4, and Eomes transcripts resulted in a loss of normal colony morphology and down-regulation of TS cell-specific genes, suggesting an important role for TCFAP2C, SMARCA4, and EOMES in TS cell self-renewal. Through genome-wide mapping and global expression analysis of five TF target genes, our data provide a comprehensive analysis of transcriptional networks that regulate TS cell self-renewal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Proliferation
  • Cells, Cultured
  • Chromatin Immunoprecipitation
  • DNA Helicases / genetics
  • DNA Helicases / metabolism
  • DNA Helicases / physiology*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Gene Regulatory Networks*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Models, Biological
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Nuclear Proteins / physiology*
  • Oligonucleotide Array Sequence Analysis
  • Pregnancy
  • Stem Cells / metabolism
  • Stem Cells / physiology*
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism
  • T-Box Domain Proteins / physiology*
  • Transcription Factor AP-2 / genetics
  • Transcription Factor AP-2 / metabolism
  • Transcription Factor AP-2 / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*
  • Trophoblasts / cytology
  • Trophoblasts / metabolism
  • Trophoblasts / physiology*


  • Eomes protein, mouse
  • Nuclear Proteins
  • T-Box Domain Proteins
  • Tfap2c protein, mouse
  • Transcription Factor AP-2
  • Transcription Factors
  • Smarca4 protein, mouse
  • DNA Helicases