C/EBP regulates the promoter of the eosinophil-derived neurotoxin/RNS2 gene in human eosinophilic cells.
The eosinophil-derived neurotoxin (EDN), a member of the mammalian ribonuclease family, is found in the large specific granules of human eosinophilic leukocytes. We have investigated the role of the C/EBP transcription factor family in the regulation of EDN promoter activity. Here we show that the C/EBP family is involved in intrinsic regulation of EDN promoter activity. We have identified a C/EBP binding site located at -124 in the proximal promoter of the EDN gene. Mutation of this C/EBP site results in a decrease of promoter activity in HL-60-eos cells as well as in eosinophils differentiated in vitro from CD34+ cells. Different C/EBP proteins are able to bind to the C/EBP site as shown by gel shift assay. Our results indicate the importance of the C/EBP family in the regulation of the EDN gene in eosinophils.
Baltus
B
B
Department of Pulmonary Diseases, University Hospital Utrecht, The Netherlands.
Buitenhuis
M
M
van Dijk
T B
TB
Vinson
C
C
Raaijmakers
J A
JA
Lammers
J W
JW
Koenderman
L
L
de Groot
R P
RP
D000818:Animals; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins; D019556:COS Cells; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D047208:Eosinophil-Derived Neurotoxin; D004804:Eosinophils / Q000502:physiology*; D005786:Gene Expression Regulation; D018922:HL-60 Cells; D006801:Humans; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D012260:Ribonucleases
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011506:Proteins; D047208:Eosinophil-Derived Neurotoxin; D012260:Ribonucleases; C479221:RNASE2 protein, human