Poster Presentation 6th Annual Meeting for Australasian Society for Stem Cell Research 2013

Krüppel-Like Factor 3 in Embryonic Stem Cell Renewal (#119)

Jessica Fittock 1 2 3 , Wei Shan Yuen 3 4 , Michael R Tallack 1 , Graham W Magor 1 , Andrew C Perkins 1
  1. Cancer Genomics, Mater Research, TRI, Woolloongabba, QLD, Australia
  2. School of Biomedical Science, University of Queensland, St Lucia, QLD, Australia
  3. Institute for Molecular Bioscience, University of Queensland, St Lucia, QLD, Australia
  4. Centre for Reproductive Science, University of Newcastle

The Krüppel-Like Factors (KLFs) are a family of transcription factor proteins that are defined by their ability to bind DNA through a C2H2-type zinc finger domain¹. KLF3 is a ubiquitously expressed member of this family which recruits the cofactor, CtBP and exhibits strong repressor activity2. The transcriptional activator, KLF4, which is closely related to KLF3 and binds the same DNA sequence, has been shown to have an important role in maintenance of the embryonic stem cell (ESC) state and the production of induced pluripotent stem cells (iPSCs)3,4. We have shown that both Klf3 and Klf4 are expressed in similar patterns during ESC differentiation and are likely to competitively bind many promoter and enhancer regions to influence the transcription of target genes5. We suggest KLF3 plays an important role in balancing self renewal and differentiation in ESCs. We have identified a novel KLF3 enhancer by ChIP-seq and investigated its function in vitro and in vivo. We have shown that KLF3 and KLF4 competitively bind this enhancer. Our contribution to an increased understanding of how the KLF family functions in ESCs and iPSCs and may ultimately assist in improving reprogramming techniques.

References

  1. Kaczynski, J., Cook, T. and Urrutia, R. 2003. Sp1 and Krüppel-like transcription factors. Genome Biology, 4.
  2. Turner, J. and Crossley, M. 1998. Cloning and characterisation of mCtBP2, a corepressor that associates with basic Krüppel-like factor and other mammalian transcriptional regulators. Embo Journal, 17, 5129-5140.
  3. Jiang, J. M., Chan, Y. S., Loh, Y. H., Cai, J., Tong, G. Q., Lim, C. A., Robson, P., Zhong, S. and NG, H. H. 2008. A core Klf circuitry regulates self renewal of embryonic stem cells. Nature Cell Biology, 10, 353-U103
  4. Takahashi, K. and Yamanaka, S. 2006. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126, 663-676.
  5. Bruce, S. J., Gardiner, B. B., Burke, L.J., Gongora, M., Grimmond, S. M. and Perkins, A. C.2007. Dynamic transcription programs during ES cell differentiation towards mesoderm in serum versus serum-free(BMP4) culture. BMC Genomics, 8, Article No.: 365