Cyclic AMP Responsive Element Binding Proteins Are Involved in 'Emergency' Granulopoiesis through the Upregulation of CCAAT/Enhancer Binding Protein β

Hideyo Hirai, Naoka Kamio, Gang Huang, Akiko Matsusue, Shinpei Ogino, Nobuhiko Kimura, Sakiko Satake, Eishi Ashihara, Jiro Imanishi, Daniel G. Tenen, Taira Maekawa

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish (US)
Article numbere54862
JournalPloS one
Volume8
Issue number1
DOIs
StatePublished - Jan 30 2013
Externally publishedYes

ASJC Scopus subject areas

  • General

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