title: Cyclic AMP responsive element binding proteins are involved in 'emergency' granulopoiesis through the upregulation of CCAAT/enhancer binding protein β.
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.
authors: Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto, Japan. hhirai@kuhp.kyoto-u.ac.jp
authors: Hideyo
authors: H
authors: Hirai
authors: Naoka
authors: N
authors: Kamio
authors: Gang
authors: G
authors: Huang
authors: Akiko
authors: A
authors: Matsusue
authors: Shinpei
authors: S
authors: Ogino
authors: Nobuhiko
authors: N
authors: Kimura
authors: Sakiko
authors: S
authors: Satake
authors: Eishi
authors: E
authors: Ashihara
authors: Jiro
authors: J
authors: Imanishi
authors: Daniel G
authors: DG
authors: Tenen
authors: Taira
authors: T
authors: Maekawa
mesh_terms: D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D023061:Gene Order; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006098:Granulocytes / Q000378:metabolism*; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D038042:Myelopoiesis / Q000502:physiology*; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D015398:Signal Transduction; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D017362:Cyclic AMP Response Element-Binding Protein; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
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