PLoS Neglected Tropical Diseases (Jan 2008)

Targets of the Entamoeba histolytica transcription factor URE3-BP.

  • Carol A Gilchrist,
  • Duza J Baba,
  • Yan Zhang,
  • Oswald Crasta,
  • Clive Evans,
  • Elisabet Caler,
  • Bruno W S Sobral,
  • Christina B Bousquet,
  • Megan Leo,
  • Ameilia Hochreiter,
  • Sarah K Connell,
  • Barbara J Mann,
  • William A Petri

DOI
https://doi.org/10.1371/journal.pntd.0000282
Journal volume & issue
Vol. 2, no. 8
p. e282

Abstract

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The Entamoeba histolytica transcription factor Upstream Regulatory Element 3-Binding Protein (URE3-BP) is a calcium-responsive regulator of two E. histolytica virulence genes, hgl5 and fdx1. URE3-BP was previously identified by a yeast one-hybrid screen of E. histolytica proteins capable of binding to the sequence TATTCTATT (Upstream Regulatory Element 3 (URE3)) in the promoter regions of hgl5 and fdx1. In this work, precise definition of the consensus URE3 element was performed by electrophoretic mobility shift assays (EMSA) using base-substituted oligonucleotides, and the consensus motif validated using episomal reporter constructs. Transcriptome profiling of a strain induced to produce a dominant-positive URE3-BP was then used to identify additional genes regulated by URE3-BP. Fifty modulated transcripts were identified, and of these the EMSA defined motif T[atg]T[tc][cg]T[at][tgc][tg] was found in over half of the promoters (54% p<0.0001). Fifteen of the URE3-BP regulated genes were potential membrane proteins, suggesting that one function of URE3-BP is to remodel the surface of E. histolytica in response to a calcium signal. Induction of URE3-BP leads to an increase in tranwell migration, suggesting a possible role in the regulation of cellular motility.