Computational promoter analysis of mouse, rat and human antimicrobial peptide-coding genes.
BACKGROUND
Mammalian antimicrobial peptides (AMPs) are effectors of the innate immune response. A multitude of signals coming from pathways of mammalian pathogen/pattern recognition receptors and other proteins affect the expression of AMP-coding genes (AMPcgs). For many AMPcgs the promoter elements and transcription factors that control their tissue cell-specific expression have yet to be fully identified and characterized.


RESULTS
Based upon the RIKEN full-length cDNA and public sequence data derived from human, mouse and rat, we identified 178 candidate AMP transcripts derived from 61 genes belonging to 29 AMP families. However, only for 31 mouse genes belonging to 22 AMP families we were able to determine true orthologous relationships with 30 human and 15 rat sequences. We screened the promoter regions of AMPcgs in the three species for motifs by an ab initio motif finding method and analyzed the derived promoter characteristics. Promoter models were developed for alpha-defensins, penk and zap AMP families. The results suggest a core set of transcription factors (TFs) that regulate the transcription of AMPcg families in mouse, rat and human. The three most frequent core TFs groups include liver-, nervous system-specific and nuclear hormone receptors (NHRs). Out of 440 motifs analyzed, we found that three represent potentially novel TF-binding motifs enriched in promoters of AMPcgs, while the other four motifs appear to be species-specific.


CONCLUSIONS
Our large-scale computational analysis of promoters of 22 families of AMPcgs across three mammalian species suggests that their key transcriptional regulators are likely to be TFs of the liver-, nervous system-specific and NHR groups. The computationally inferred promoter elements and potential TF binding motifs provide a rich resource for targeted experimental validation of TF binding and signaling studies that aim at the regulation of mouse, rat or human AMPcgs.
Brahmachary
Manisha
M
Knowledge Extraction Laboratory, Institute for Infocomm Research, 21 Heng Mui Keng Terrace, Singapore 119613, Singapore. manisha@i2r.a-star.edu.sg
Schönbach
Christian
C
Yang
Liang
L
Huang
Enli
E
Tan
Sin Lam
SL
Chowdhary
Rajesh
R
Krishnan
S P T
SP
Lin
Chin-Yo
CY
Hume
David A
DA
Kai
Chikatoshi
C
Kawai
Jun
J
Carninci
Piero
P
Hayashizaki
Yoshihide
Y
Bajic
Vladimir B
VB
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics*; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics; D019295:Computational Biology / Q000379:methods*; D004745:Enkephalins / Q000235:genetics; D006801:Humans; D051379:Mice; D005810:Multigene Family / Q000235:genetics; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000235:genetics; D016601:RNA-Binding Proteins; D051381:Rats; D017422:Sequence Analysis, DNA / Q000379:methods*; D014157:Transcription Factors / Q000378:metabolism; D023084:alpha-Defensins / Q000235:genetics
D023181:Antimicrobial Cationic Peptides; D002352:Carrier Proteins; D004745:Enkephalins; D011498:Protein Precursors; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C465959:Zc3hav1 protein, rat; D023084:alpha-Defensins; C029992:proenkephalin