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- Title
Proteomic identification of the MYST domain histone acetyltransferase TIP60 (HTATIP) as a co-activator of the myeloid transcription factor C/EBPalpha.
- Authors
Bararia, D.; Trivedi, A. K.; Zada, A. A. Peer; Greif, P. A.; Mulaw, M. A.; Christopeit, M.; Hiddemann, W.; Bohlander, S. K.; Behre, G.
- Abstract
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.
- Subjects
PROTEOMICS; HISTONES; ACETYLTRANSFERASES; TRANSCRIPTION factors; LEUKEMIA etiology; PROTEINS; MASS spectrometry; CHROMATIN; PROTEIN metabolism; RNA analysis; CELL differentiation; CELL lines; CELLS; COMPARATIVE studies; GENES; RESEARCH methodology; MEDICAL cooperation; MOLECULAR structure; RESEARCH; TRANSFERASES; EVALUATION research
- Publication
Leukemia (08876924), 2008, Vol 22, Issue 4, p800
- ISSN
0887-6924
- Publication type
journal article
- DOI
10.1038/sj.leu.2405101