Transcriptional targets of Foxd3 in murine ES cells

Stem Cell Res. 2014 Jan;12(1):233-40. doi: 10.1016/j.scr.2013.10.008. Epub 2013 Nov 5.

Abstract

Understanding gene regulatory networks controlling properties of pluripotent stem cells will facilitate development of stem cell-based therapies. The transcription factor Foxd3 is critical for maintenance of self-renewal, survival, and pluripotency in murine embryonic stem cells (ESCs). Using a conditional deletion of Foxd3 followed by gene expression analyses, we demonstrate that genes required for several developmental processes including embryonic organ development, epithelium development, and epithelial differentiation were misregulated in the absence of Foxd3. Additionally, we identified 6 novel targets of Foxd3 (Sox4, Safb, Sox15, Fosb, Pmaip1 and Smarcd3). Finally, we present data suggesting that Foxd3 functions upstream of genes required for skeletal muscle development. Together, this work provides further evidence that Foxd3 is a critical regulator of murine development through the regulation of lineage specific differentiation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Line
  • Chromatin Immunoprecipitation
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism
  • Cluster Analysis
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism
  • Forkhead Transcription Factors / deficiency
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression Regulation, Developmental
  • Matrix Attachment Region Binding Proteins / genetics
  • Matrix Attachment Region Binding Proteins / metabolism
  • Mice
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism
  • Muscle, Skeletal / growth & development
  • Muscle, Skeletal / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • Repressor Proteins / deficiency
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • SOX Transcription Factors / genetics
  • SOX Transcription Factors / metabolism
  • SOXC Transcription Factors / genetics
  • SOXC Transcription Factors / metabolism

Substances

  • Chromosomal Proteins, Non-Histone
  • Forkhead Transcription Factors
  • Fosb protein, mouse
  • Foxd3 protein, mouse
  • Matrix Attachment Region Binding Proteins
  • Muscle Proteins
  • Pmaip1 protein, mouse
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-fos
  • Repressor Proteins
  • SOX Transcription Factors
  • SOXC Transcription Factors
  • Smarcd3 protein, mouse
  • Sox15 protein, mouse
  • Sox4 protein, mouse