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

被引：40

作者：

Bararia, D. ^{[2
,3
]}

Trivedi, A. K. ^{[1
]}

Zada, A. A. Peer ^{[1
]}

Greif, P. A. ^{[2
,3
]}

Mulaw, M. A. ^{[2
,3
]}

Christopeit, M. ^{[1
]}

Hiddemann, W. ^{[2
,3
]}

Bohlander, S. K. ^{[2
,3
]}

Behre, G. ^{[1
]}

机构：

[1] Univ Halle Wittenberg, Bone Marrow Transplantat Sect, Dept Hematol & Oncol, D-06097 Halle, Germany

[2] Univ Munich, Dept Med 3, Munich, Germany

[3] German Res Ctr Environm Hlth, Clin Cooperat Grp, HelmholtzZentrum, Munich, Germany

来源：

LEUKEMIA | 2008年 / 22卷 / 04期

关键词：

C/EBP alpha; HTATIP; mass spectrometry; AML;

D O I：

10.1038/sj.leu.2405101

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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

引用

页码：800 / 807

页数：8

共 27 条

[1]

Stimulation of CREB binding protein nucleosomal histone acetyltransferase activity by a class of transcriptional activators [J].