PU.1-mediated transcriptional regulation of prophenin-2 in primary bone marrow cells

• Published in: Gene Vol. 352; pp. 1 - 9
• Main Authors: Ramanathan, Balaji, Minton, J. Ernest, Ross, Chris R., Blecha, Frank
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 06.06.2005
• Subjects: Animals; Base Sequence; Binding Sites - genetics; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; Cathelicidin; Cells, Cultured; Cloning, Molecular; DNA, Complementary - chemistry; DNA, Complementary - genetics; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology; HeLa Cells; Humans; Immune-regulation; Innate immunity; Interleukin-3 - pharmacology; Luciferases - genetics; Luciferases - metabolism; Mice; Molecular Sequence Data; Mutation; Promoter Regions, Genetic - genetics; Proteins - genetics; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Regulatory Sequences, Nucleic Acid - genetics; Sequence Analysis, DNA; Sus scrofa; Swine; Trans-Activators - genetics; Trans-Activators - metabolism; Transcriptional Activation - drug effects; Transcriptional regulation; Transfection; C/EBP; LL-37; DMSO; NF-kB; Innate immunity; AP-2; Transcriptional regulation; CFU; CREB; GM-CSF; Sp1; RT-PCR; FBS; NF-IL6; cDNA; PR-39; Immune-regulation; LFA-1; c-Myb; EST; oligo (dT); IL-3; DNAase; Cathelicidin; STAT; T-box factor; TNF-α; RLM-RACE; TESS; MZF-1; BPI; AML-1; RPMI; PF-2; PCR
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2005.04.011

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.