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  • Original Paper
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Identification of a Myb-responsive enhancer of the chicken C/EBPβ gene

Oncogene volume 23, pages 5807–5814 (2004)Cite this article

Abstract

The retroviral oncogene v-myb encodes a transcription factor (v-Myb) that disrupts myelomonocytic differentiation and transforms myelomonocytic cells. It is thought that the biological effects of v-Myb are caused by deregulation of specific target genes. The CCAAT box/enhancer binding protein beta (C/EBPβ), a member of the basic region-leucine zipper (bzip) class of transcription factors, which itself plays an important role during myelomonocytic differentiation, has previously been shown to be regulated by Myb. Here we have addressed the mechanism by which v-Myb affects C/EBPβ expression. We have employed the mapping of DNase I hypersensitive sites (DHSs) in chromatin as a tool to detect in vivo target sites of v-Myb. Our data identify a DHS downstream of the C/EBPβ gene that appears to be specific for v-myb-transformed myeloblasts. We have confirmed by chromatin immunoprecipitation that v-Myb is bound to this region in vivo. Furthermore, we have found that ectopic expression of v-Myb in a myelomonocytic cell line is able to induce a DHS downstream of the C/EBPβ gene, showing for the first time that v-Myb can affect chromatin structure. Reporter gene experiments demonstrate that the downstream DHS acts as a Myb-dependent enhancing element in transiently as well as in stably transfected myelomonocytic cells. Previous work has shown that v-Myb acts on the C/EBPβ promoter; it now appears that Myb stimulates C/EBPβ expression by acting on the promoter as well as on an enhancer of the C/EBPβ gene. Interestingly, the mechanisms by which Myb acts on both elements differ; while Myb activation of the promoter requires the cooperation with C/EBPβ, activation of the enhancer by Myb is independent of C/EBPβ. Apart from the identification of a novel Myb-dependent enhancer, our work demonstrates the potential of chromatin structure analysis for the identification of Myb target sites.

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Acknowledgements

We thank A Brehmer-Fastnacht for expert technical assistance and the members of our group for discussions. This work was supported by the DFG (SFB 293 and Kl 461/10-1). VY was supported by a fellowship from the Ministry of University Affairs, Thailand. DB was supported by the Studienstiftung des Deutschen Volkes and the Fonds der chemischen Industrie, which is financed, in part, by the BMBF.

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  1. Institut für Biochemie, Westfälische-Wilhelms-Universität Münster, Wilhelm-Klemm-Str. 2, Münster, D-48149, Germany

    Jörg Kintscher, Vichanan Yamkamon, Daniel Braas & Karl-Heinz Klempnauer

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  1. Jörg Kintscher
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  2. Vichanan Yamkamon
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  3. Daniel Braas
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  4. Karl-Heinz Klempnauer
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Correspondence to Karl-Heinz Klempnauer.

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Kintscher, J., Yamkamon, V., Braas, D. et al. Identification of a Myb-responsive enhancer of the chicken C/EBPβ gene. Oncogene 23, 5807–5814 (2004). https://doi.org/10.1038/sj.onc.1207722

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