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Proteomic identification of the MYST domain histone acetyltransferase TIP60 (HTATIP) as a co-activator of the myeloid transcription factor C/EBPalpha.

The transcription factor C/EBPalpha (CEBPA) is a key player in granulopoiesis and leukemogenesis. We have previously reported the interaction of C/EBPalpha with other proteins (utilizing mass spectrometry) in transcriptional regulation. In the present study, we characterized the association of the MYST domain histone acetyltransferase Tat-interactive protein (TIP) 60 (HTATIP) with C/EBPalpha. We show in pull-down and co-precipitation experiments that C/EBPalpha and HTATIP interact. A chromatin immunoprecipitation (ChIP) and a confirmatory Re-ChIP assay revealed in vivo occupancy of the C/EBPalpha and GCSF-R promoter by HTATIP. Reporter gene assays showed that HTATIP is a co-activator of C/EBPalpha. The co-activator function of HTATIP is dependent on its intact histone acetyltransferase (HAT) domain and on the C/EBPalpha DNA-binding domain. The resulting balance between histone acetylation and deacetylation at the C/EBPalpha promoter might represent an important mechanism of C/EBPalpha action. We observed a lower expression of HTATIP mRNA in undifferentiated U937 cells compared to retinoic acid-induced differentiated U937 cells, and correlated expression of CEBPA and HTATIP mRNA levels were observed in leukemia samples. These findings point to a functional synergism between C/EBPalpha and HTATIP in myeloid differentiation and suggest that HTATIP might be an important player in leukemogenesis.

Pubmed ID: 18239623

Authors

  • Bararia D
  • Trivedi AK
  • Zada AA
  • Greif PA
  • Mulaw MA
  • Christopeit M
  • Hiddemann W
  • Bohlander SK
  • Behre G

Journal

Leukemia

Publication Data

April 16, 2008

Associated Grants

None

Mesh Terms

  • CCAAT-Enhancer-Binding Protein-alpha
  • Cell Differentiation
  • Cell Line
  • Histone Acetyltransferases
  • Humans
  • Myeloid Cells
  • Promoter Regions, Genetic
  • Protein Interaction Domains and Motifs
  • Proteomics
  • RNA, Messenger