Identification and characterization of the Myb-inducible promoter of the chicken adenosine receptor 2B gene

Kattmann, Dana; Klempnauer, Karl‐Heinz

doi:10.1038/sj.onc.1205579

Cited by 9 publications

(8 citation statements)

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“…The regulation of the chicken C/EBP␤ gene, another Myb target, has recently been analyzed (29,41), and it was found that v-Myb acts on the C/EBP␤ promoter as well as on a cell-specific enhancer located downstream of the gene (21). The chicken adenosine receptor 2B gene, another Myb target (19,49), also has a Myb-responsive promoter and, additionally, a Myb-responsive enhancer (unpublished observations). Thus, that v-Myb activates downstream targets by acting on two separate regions of these genes may be a more common phenomenon.…”

Section: Discussionmentioning

confidence: 99%

v-Myb Mediates Cooperation of a Cell-Specific Enhancer with the mim-1 Promoter

Chayka

Kintscher

Braas

et al. 2005

Molecular and Cellular Biology

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The oncogenic transcription factor v-Myb disrupts myelomonocytic differentiation and transforms myelomonocytic cells by deregulating the expression of specific target genes. One of these genes, the chicken mim-1 gene, is activated by Myb exclusively in myelomonocytic cells and, therefore, has been an interesting model system to study how Myb activates a target in a lineage-specific manner. Previous work has suggested that Myb activates mim-1 by cooperating with CCAAT box/enhancer binding protein beta (C/EBP␤) or other C/EBP transcription factors at the mim-1 promoter. We have now identified and characterized a powerful Mybdependent enhancer located 2 kb upstream of the mim-1 promoter. The enhancer is preferentially active in myelomonocytic cells, confers Myb responsiveness onto a heterologous promoter, and dramatically increases Myb responsiveness of the mim-1 promoter. Chromatin immunoprecipitation demonstrates that v-Myb and C/EBP␤ are bound to the enhancer in v-Myb-transformed cells; furthermore, cooperation of the enhancer with the mim-1 promoter is greatly stimulated by C/EBP␤ and p300. Taken together, our results show that the regulation of mim-1 expression by v-Myb is more complex than previously assumed and involves two distinct regions of the mim-1 gene. A major function of v-Myb (in addition to its role at the mim-1 promoter) apparently is to activate the mim-1 enhancer and, together with C/EBP␤ and p300, facilitate its cooperation with the promoter. Interestingly, our work also shows that the v-Myb protein encoded by avian myeloblastosis virus is defective in this function, suggesting an explanation for why primary avian myeloblastosis virus-transformed myeloblasts do not express the mim-1 gene.

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Section: Discussionmentioning

confidence: 99%

v-Myb Mediates Cooperation of a Cell-Specific Enhancer with the mim-1 Promoter

Chayka

Kintscher

Braas

et al. 2005

Molecular and Cellular Biology

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“…19 The total amount of DNA was adjusted with empty vector (pEGFP-C1). For ligand stimulation, cells were treated with 1 mM ATRA and/or 1 mM valproic acid (VPA) for 16 h. Data were plotted relative to b-galactosidase activity.…”

Section: Transient Transfections and Reporter Gene Assaysmentioning

confidence: 99%

Inhibition of retinoic acid receptor signaling by Ski in acute myeloid leukemia

et al. 2006

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Acute myeloid leukemia (AML) is a heterogeneous disease with multiple different cytogenetic and molecular aberrations contributing to leukemic transformation. We compared gene expression profiles of 4608 genes using cDNA-arrays from 20 AML patients (nine with À7/del7q and 11 with normal karyotype) with 23 CD34 þ preparations from healthy bone marrow donors. SKI, a nuclear oncogene, was highly up regulated. In a second set of 183 AML patients analyzed with real-time PCR, the highest expression level of SKI in AML with À7/del7q could be confirmed. As previously described, Ski associates with the retinoic acid receptor (RAR) complex and can repress transcription. We wanted to investigate the interference of Ski with RARa signaling in AML. Ski was co-immunoprecipitated and colocalized with RARa. We also found that overexpression of wild-type Ski inhibited the prodifferentiating effects of retinoic acid in U937 leukemia cells. Mutant Ski, lacking the N-CoR binding, was no more capable of repressing RARa signaling. The inhibition by wild-type Ski could partially be reverted by the histone deacetylase blocking agent valproic acid. In conclusion, Ski seems to be involved in the blocking of differentiation in AML via inhibition of RARa signaling.

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“…20 c-Myb is strongly associated with cell proliferation and G 1 /S transitions 21 and functions via binding to a consensus DNA sequence (TAAC T/G T/G) in the promoters of Myb-dependent genes. 22 c-Myb is known to regulate the promoters of key cell cycle genes such as c-myc (5 Myb binding sites 23 ), cyclin A1, and cdk1 (2 sites each 24,25 ), proliferation-enabling enzymes such as DNA topoisomerase II ␣ and methionine adenosyltransferase-2A (1 site each 26,27 ), a G protein-coupled receptor (adenosine receptor 2B; 33 sites 28 ) involved in endothelial cell proliferation, and Ca 2ϩ transporters such as PMCA1 (2 sites 29 ) known to be involved in VSMC proliferation. We and others have previously shown that c-Myb-dependent transcription has a significant role in regulating [Ca 2ϩ ] i at the G 1 /S transition of VSMCs 9,29,30 .…”

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confidence: 99%