Genesis, a winged helix transcriptional repressor with expression restricted to embryonic stem cells

Jill Sutton, Robert Costa, Michael Klug, Loren Field, Dawei Xu, David A. Largaespada, Colin F. Fletcher, Nancy A. Jenkins, Neal G. Copeland, Michael Klemsz, Robert Hromas

Research output: Contribution to journalArticle

156 Scopus citations

Abstract

A novel member of the winged helix (formerly HNF-3/Forkhead) transcriptional regulatory family, termed Genesis, was isolated and characterized. Putative translation of the complete cDNA revealed the winged helix DNA binding domain to be centrally located within the protein, with regions on either side that contain known transcriptional regulatory motifs. Extensive Northern analysis of Genesis found that the message was exclusively expressed in embryonic stem cells or their malignant equivalent, embryonal carcinoma cells. The Genesis transcript was down-regulated when these cells were stimulated to differentiate. DNA sequences that Genesis protein would interact with were characterized and were found to contain a consensus similar to that found in an embryonic stem cell enhancer sequence. Co- transfection experiments revealed that Genesis is a transcriptional repressor. Genesis mapped to mouse chromosome 4 in a region syntenic with human chromosome 1p31, a site of nonrandom abnormalities in germ cell neoplasia, neuroblastoma, and acute lymphoblastic leukemia. Genesis is a candidate for regulating the phenotype of normal or malignant embryonic stem cells.

Original languageEnglish (US)
Pages (from-to)23126-23133
Number of pages8
JournalJournal of Biological Chemistry
Volume271
Issue number38
DOIs
StatePublished - 1996

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Sutton, J., Costa, R., Klug, M., Field, L., Xu, D., Largaespada, D. A., Fletcher, C. F., Jenkins, N. A., Copeland, N. G., Klemsz, M., & Hromas, R. (1996). Genesis, a winged helix transcriptional repressor with expression restricted to embryonic stem cells. Journal of Biological Chemistry, 271(38), 23126-23133. https://doi.org/10.1074/jbc.271.38.23126