c/EBPbeta is a major regulatory element driving transcriptional activation of the CXCL12 promoter.
CXCL12 is considered a constitutively expressed chemokine with homeostatic functions. However, induction of CXCL12 expression and its potential role in several pathologic conditions have been reported, suggesting that CXCL12 gene expression can be induced by different stimuli. To elucidate the molecular mechanisms involved in the regulation of CXCL12 gene expression, we aim to define the molecular factors that operate at the transcriptional level. Basal, constitutive expression of CXCL12 was dependent on basic helix-loop-helix factors. Transcriptional up-regulation of the CXCL12 gene was induced by cellular confluence or inflammatory stimuli such as interleukin-1 and interleukin-6, in a CCAAT/enhancer binding protein beta (c/EBPbeta)-dependent manner. Chromatin immunoprecipitation assays confirmed c/EBPbeta binding to a specific response element located at -1171 of the promoter region of CXCL12. Our data show that c/EBPbeta is a major regulatory element driving transcription of the CXCL12 gene in response to cytokines and cell confluence.
Calonge
E
E
AIDS Immunopathology Unit, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Ctra. Majadahonda-Pozuelo, Km 2, 28220 Majadahonda, Madrid, Spain.
Alonso-Lobo
J M
JM
Escandón
C
C
González
N
N
Bermejo
M
M
Santiago
B
B
Mestre
L
L
Pablos
J L
JL
Caruz
A
A
Alcamí
J
J
D001483:Base Sequence; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000096:biosynthesis*; D047369:Chromatin Immunoprecipitation; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020218:Response Elements; D015533:Transcriptional Activation
D022782:CCAAT-Enhancer-Binding Protein-beta; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D016207:Cytokines; D004247:DNA