title: Triaging informative cis-regulatory elements for the combinatorial control of temporal gene expression during Plasmodium falciparum intraerythrocytic development.
abstract: BACKGROUND
  Over 2700 genes are subject to stage-specific regulation during the intraerythrocytic development of the human malaria parasite Plasmodium falciparum. Bioinformatic analyses have identified a large number of over-represented motifs in the 5' flanking regions of these genes that may act as cis-acting factors in the promoter-based control of temporal expression. Triaging these lists to provide candidates most likely to play a role in regulating temporal expression is challenging, but important if we are to effectively design in vitro studies to validate this role.
  
  
  METHODS
  We report here the application of a repeated search of variations of 5' flanking sequences from P. falciparum using the Finding Informative Regulatory Elements (FIRE) algorithm.
  
  
  RESULTS
  Our approach repeatedly found a short-list of high scoring DNA motifs, for which cognate specific transcription factors were available, that appear to be typically associated with upregulation of mRNA accumulation during the first half of intraerythrocytic development.
  
  
  CONCLUSIONS
  We propose these cis-trans interactions may provide a combinatorial promoter-based control of gene expression to complement more global mechanisms of gene regulation that can account for temporal control during the second half of intraerythrocytic development.
authors: Institute for Science and Technology in Medicine, Keele University, Staffordshire, ST5 5BG, UK. k.t.russell@keele.ac.uk.
authors: Karen
authors: K
authors: Russell
authors: School of Veterinary Medicine and Science, University of Nottingham, Leicestershire, LE12 5RD, UK. richard.emes@nottingham.ac.uk.|Advanced Data Analysis Centre, University of Nottingham, Leicestershire, LE12 5RD, UK. richard.emes@nottingham.ac.uk.
authors: Richard
authors: R
authors: Emes
authors: Institute for Science and Technology in Medicine, Keele University, Staffordshire, ST5 5BG, UK. p.d.horrocks@keele.ac.uk.
authors: Paul
authors: P
authors: Horrocks
mesh_terms: D019295:Computational Biology; D004912:Erythrocytes / Q000469:parasitology*; D005786:Gene Expression Regulation; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000235:genetics* / Q000254:growth & development* / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional
chemical_list: D015800:Protozoan Proteins
references: Mol Microbiol. 2009 Mar;71(6):1402-14
references: 19220746
references: Bioinformatics. 2009 Jun 15;25(12):1484-91
references: 19336444
references: BMC Genomics. 2009;10:610
references: 20015349
references: Nat Biotechnol. 2010 Jan;28(1):91-8
references: 20037583
references: J Mol Biol. 2010 Jan 22;395(3):558-67
references: 19913037
references: Genome Res. 2010 Feb;20(2):228-38
references: 20054063
references: Genome Res. 2004 Nov;14(11):2308-18
references: 15520293
references: BMC Genomics. 2014;15:347
references: 24885191
references: Nucleic Acids Res. 2005;33(13):3994-4006
references: 16040597
references: Trends Genet. 2006 Feb;22(2):73-8
references: 16380193
references: Nucleic Acids Res. 2006;34(4):1166-73
references: 16493140
references: Mol Biochem Parasitol. 2007 May;153(1):19-30
references: 17307259
references: Exp Parasitol. 2007 Sep;117(1):87-92
references: 17475254
references: Am J Trop Med Hyg. 2007 Aug;77(2):201-8
references: 17690387
references: Mol Cell. 2007 Oct 26;28(2):337-50
references: 17964271
references: Genome Biol. 2007;8(7):R134
references: 17612404
references: BMC Genomics. 2008;9:70
references: 18257930
references: Proc Natl Acad Sci U S A. 2008 Jun 17;105(24):8393-8
references: 18541913
references: Bioinformatics. 2008 Sep 1;24(17):1843-9
references: 18611947
references: BMC Genomics. 2008;9:388
references: 18706115
references: Trends Parasitol. 2008 Dec;24(12):551-6
references: 18929512
references: PLoS Pathog. 2008 Nov;4(11):e1000214
references: 19023412
references: Mol Biochem Parasitol. 2002 Jun;122(1):9-19
references: 12076766
references: Science. 2003 Sep 12;301(5639):1503-8
references: 12893887
references: Cell. 2003 Dec 26;115(7):771-85
references: 14697197
references: PLoS Biol. 2003 Oct;1(1):E5
references: 12929205
references: Genome Res. 2004 Aug;14(8):1548-54
references: 15256513
references: Mol Biochem Parasitol. 1999 Mar 15;99(1):77-87
references: 10215026
references: Exp Parasitol. 2009 Jan;121(1):46-54
references: 18951895
references: Mol Biochem Parasitol. 2009 Mar;164(1):9-25
references: 19110008
references: Genome Biol. 2008;9(12):R178
references: 19094208
references: Eukaryot Cell. 2009 Mar;8(3):327-38
references: 19151330
references: PLoS Pathog. 2010 Feb;6(2):e1000784
references: 20195509
references: Cell Microbiol. 2010 Apr 1;12(4):413-23
references: 20109158
references: Mol Microbiol. 2010 Feb;75(4):854-63
references: 20025671
references: PLoS Pathog. 2010;6(10):e1001165
references: 21060817
references: Mol Biochem Parasitol. 2011 Mar;176(1):1-7
references: 21126543
references: Infect Genet Evol. 2011 Jun;11(4):716-24
references: 20708104
references: PLoS One. 2012;7(11):e47557
references: 23144823
references: BMC Genomics. 2013;14:267
references: 23601558
references: Nature. 2014 Mar 13;507(7491):253-7
references: 24572359
references: Nature. 2014 Mar 13;507(7491):248-52
references: 24572369
references: Genome Res. 2014 Jun;24(6):974-88
references: 24671853
references: Mol Biochem Parasitol. 2005 Sep;143(1):67-79
references: 16005087