title: Identification of novel transcriptional regulators involved in macrophage differentiation and activation in U937 cells.
abstract: BACKGROUND
  Monocytes and macrophages play essential role in innate immunity. Understanding the underlying mechanism of macrophage differentiation and the identification of regulatory mechanisms will help to find new strategies to prevent their harmful effects in chronic inflammatory diseases and sepsis.
  
  
  RESULTS
  Maturation of blood monocytes into tissue macrophages and subsequent inflammatory response was mimicked in U937 cells of human histocytic lymphoma origin. Whole genome array analysis was employed to evaluate gene expression profile to identify underlying transcriptional networks implicated during the processes of differentiation and inflammation. In addition to already known transcription factors (i.e. MAFB, EGR, IRF, BCL6, NFkB, AP1, Nur77), gene expression analysis further revealed novel genes (i.e. MEF2, BRI, HLX, HDAC5, H2AV, TCF7L2, NFIL3) previously uncharacterized to be involved in the differentiation process. A total of 58 selected genes representing cytokines, chemokines, surface antigens, signaling molecules and transcription factors were validated by real time PCR and compared to primary monocyte-derived macrophages. Beside the verification of several new genes, the comparison reveals individual heterogeneity of blood donors.
  
  
  CONCLUSIONS
  Up regulation of MEF2 family, HDACs, and H2AV during cell differentiation and inflammation sheds new lights onto regulation events on transcriptional and epigenetic level controlling these processes. Data generated will serve as a source for further investigation of macrophages differentiation pathways and related biological responses.
authors.affiliation: Department of Vertebrate Genomics, Max-Planck-Institute for Molecular Genetics, 14195 Berlin, Germany. baek@molgen.mpg.de
authors.forename: Young-Sook
authors.initials: YS
authors.lastname: Baek
authors.forename: Stefan
authors.initials: S
authors.lastname: Haas
authors.forename: Holger
authors.initials: H
authors.lastname: Hackstein
authors.forename: Gregor
authors.initials: G
authors.lastname: Bein
authors.forename: Maria
authors.initials: M
authors.lastname: Hernandez-Santana
authors.forename: Hans
authors.initials: H
authors.lastname: Lehrach
authors.forename: Sascha
authors.initials: S
authors.lastname: Sauer
authors.forename: Harald
authors.initials: H
authors.lastname: Seitz