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
DNA material CS-CDF-EG-PRE (RDB04380)