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Oncogenes, Fusion Genes and Tumor Suppressor Genes

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

Leukemia volume 22, pages 800–807 (2008)Cite this article

Abstract

The transcription factor C/EBPα (CEBPA) is a key player in granulopoiesis and leukemogenesis. We have previously reported the interaction of C/EBPα 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/EBPα. We show in pull-down and co-precipitation experiments that C/EBPα and HTATIP interact. A chromatin immunoprecipitation (ChIP) and a confirmatory Re-ChIP assay revealed in vivo occupancy of the C/EBPα and GCSF-R promoter by HTATIP. Reporter gene assays showed that HTATIP is a co-activator of C/EBPα. The co-activator function of HTATIP is dependent on its intact histone acetyltransferase (HAT) domain and on the C/EBPα DNA-binding domain. The resulting balance between histone acetylation and deacetylation at the C/EBPα promoter might represent an important mechanism of C/EBPα 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/EBPα and HTATIP in myeloid differentiation and suggest that HTATIP might be an important player in leukemogenesis.

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Acknowledgements

This study was supported by a scholarship of the Deutsche José Carreras Leukämie-Stiftung e.V. to DB, and by BMBF grants to GB (NGFN2: WP3-SP14) and SKB (NGFN2: WP3-SP11).

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Author notes

  1. S K Bohlander and G Behre: Joint senior authors.

Authors and Affiliations

  1. Department of Medicine III, University of Munich and Clinical Cooperative Group, HelmholtzZentrum ‘German Research Center for Environmental Health’, Munich, Germany

    D Bararia, P A Greif, M A Mulaw, W Hiddemann & S K Bohlander

  2. Department of Hematology and Oncology, Bone Marrow Transplantation Section, Martin-Luther-University Halle-Wittenberg, Halle, Germany

    A K Trivedi, A A Peer Zada, M Christopeit & G Behre

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  1. D Bararia
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Correspondence to S K Bohlander or G Behre.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Bararia, D., Trivedi, A., Zada, A. et al. Proteomic identification of the MYST domain histone acetyltransferase TIP60 (HTATIP) as a co-activator of the myeloid transcription factor C/EBPα. Leukemia 22, 800–807 (2008). https://doi.org/10.1038/sj.leu.2405101

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