RRC ID |
67693
|
Author |
Hirai H, Kamio N, Huang G, Matsusue A, Ogino S, Kimura N, Satake S, Ashihara E, Imanishi J, Tenen DG, Maekawa T.
|
Title |
Cyclic AMP responsive element binding proteins are involved in 'emergency' granulopoiesis through the upregulation of CCAAT/enhancer binding protein β.
|
Journal |
PLoS One
|
Abstract |
In contrast to the definitive role of the transcription factor, CCAAT/Enhancer binding protein α (C/EBPα), in steady-state granulopoiesis, previous findings have suggested that granulopoiesis during emergency situations, such as infection, is dependent on C/EBPβ. In this study, a novel lentivirus-based reporter system was developed to elucidate the molecular switch required for C/EBPβ-dependency. The results demonstrated that two cyclic AMP responsive elements (CREs) in the proximal promoter region of C/EBPβ were involved in the positive regulation of C/EBPβ transcription during granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced differentiation of bone marrow cells. In addition, the transcripts of CRE binding (CREB) family proteins were readily detected in hematopoietic stem/progenitor cells. CREB was upregulated, phosphorylated and bound to the CREs in response to GM-CSF stimulation. Retroviral transduction of a dominant negative CREB mutant reduced C/EBPβ mRNA levels and significantly impaired the proliferation/differentiation of granulocyte precursors, while a constitutively active form of CREB facilitated C/EBPβ transcription. These data suggest that CREB proteins are involved in the regulation of granulopoiesis via C/EBPβ upregulation.
|
Volume |
8(1)
|
Pages |
e54862
|
Published |
2013-1-1
|
DOI |
10.1371/journal.pone.0054862
|
PII |
PONE-D-11-25889
|
PMID |
23382991
|
PMC |
PMC3559830
|
MeSH |
Animals
CCAAT-Enhancer-Binding Protein-beta / genetics*
CCAAT-Enhancer-Binding Protein-beta / metabolism
Cell Line
Cyclic AMP Response Element-Binding Protein / metabolism*
Gene Expression Regulation / drug effects
Gene Order
Genes, Reporter
Genetic Vectors / genetics
Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
Granulocytes / metabolism*
Humans
Lentivirus / genetics
Mice
Myelopoiesis / physiology*
Promoter Regions, Genetic
Regulatory Sequences, Nucleic Acid
Signal Transduction
Transcriptional Activation / drug effects
|
IF |
2.74
|
Resource |
DNA material |
CS-CDF-EG-PRE (RDB04380) |