PU.1-mediated transcriptional regulation of prophenin-2 in primary bone marrow cells.
Prophenin-2 (PF-2) is a cathelicidin, 97-amino-acid antimicrobial protein stored in neutrophil secondary granules. PF-2 is expressed specifically in porcine immature myeloid cells; however, little is known about its regulation. In this study, we characterized the 5' regulatory regions of the PF-2 gene to understand the molecular mechanisms regulating its expression. Using bioinformatic approaches, site-directed mutagenesis, and transactivation experiments, we found that the PF-2 gene was regulated by transcription factor PU.1. In addition, PF-2 expression also is regulated by the cytokines GM-CSF and IL-3. Taken together, these results identify cis- and trans-acting factors involved in the regulation of PF-2 and clarify mechanisms of cathelidicin gene regulation.
Ramanathan
Balaji
B
Coles Hall 228, Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506-5802, USA.
Minton
J Ernest
JE
Ross
Chris R
CR
Blecha
Frank
F
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D017422:Sequence Analysis, DNA; D013552:Swine; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D000099232:Proto-Oncogene Protein Spi-1; D054804:Cathelicidins
D018076:DNA, Complementary; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007377:Interleukin-3; D008156:Luciferases; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C084994:NPG4 protein, Sus scrofa; D054804:Cathelicidins