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MOZ-TIF2 alters cofactor recruitment and histone modification at the RARbeta2 promoter: differential effects of MOZ fusion proteins on CBP- and MOZ-dependent activators.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2006 Jun 23; Vol. 281 (25), pp. 17124-17133. Date of Electronic Publication: 2006 Apr 13. - Publication Year :
- 2006
-
Abstract
- MOZ-TIF2 and MOZ-CBP are leukemogenic fusion proteins associated with therapy-induced acute myeloid leukemia. These proteins are thought to subvert normal gene expression in differentiating hematopoietic progenitor cells. We have previously shown that MOZ-TIF2 inhibits transcription by CREB-binding protein (CBP)/p300-dependent activators such as nuclear receptors and p53. Here we have shown that MOZ-TIF2 associates with the RARbeta2 promoter in vivo, resulting in altered recruitment of CBP/p300, aberrant histone modification, and down-regulation of the RARbeta2 gene. In contrast, MOZ-TIF2 up-regulated transcription mediated by the MOZ/MYST3-dependent activator AML1/RUNX1. Both wild type MOZ and MOZ-TIF2 were found to colocalize with AML1, and MOZ-TIF2 was recruited to an AML1 target promoter. A MOZ-CBP fusion protein showed similar functions to MOZ-TIF2 in that it inhibited retinoic acid receptor-mediated transcription but enhanced AML1 reporter activation. Although it contains almost the entire CBP sequence, MOZ-CBP does not appear to associate with PML bodies. In summary, our results indicate that leukemogenic MOZ fusion proteins have differential effects on the activities of CBP-dependent and MOZ-dependent activators because of their ability to alter cofactor recruitment and chromatin modification at target promoters.
- Subjects :
- Animals
COS Cells
Cell Line, Tumor
Chlorocebus aethiops
Core Binding Factor Alpha 2 Subunit metabolism
Humans
Oncogene Proteins, Fusion chemistry
Receptors, Retinoic Acid metabolism
Recombinant Fusion Proteins chemistry
p300-CBP Transcription Factors chemistry
Gene Expression Regulation, Neoplastic
Histones chemistry
Oncogene Proteins, Fusion physiology
Promoter Regions, Genetic
Receptors, Retinoic Acid genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 281
- Issue :
- 25
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 16613851
- Full Text :
- https://doi.org/10.1074/jbc.M602633200