The promoter regions of the Myb-regulated Adora2B and Mcm4 genes co-localize with origins of DNA replication

Holger Gundelach,Karl-Heinz Klempnauer,Daniel Braas

doi:10.1186/1471-2199-8-75

Holger Gundelach, Karl-Heinz Klempnauer + Show 1 more

Open Access

https://doi.org/10.1186/1471-2199-8-75

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Abstract

BackgroundThe retroviral oncogene v-myb encodes a transcription factor (v-Myb) which is responsible for the transformation of myelomonocytic cells by avian myeloblastosis virus (AMV). v-Myb is thought to exert its biological effects by deregulating the expression of specific target genes. We have recently demonstrated that the chicken Gas41 gene, whose promoter co-localizes with an origin of DNA replication, is a bona fide Myb target gene. Because of this finding we have asked whether other Myb-regulated genes are also associated with DNA replication origins.ResultsWe show that the promoter region of the chicken adenosine receptor 2B gene (Adora2B), a known Myb-target gene, acts as a DNA replication origin. Furthermore, we have examined known replication origins for the presence of Myb binding sites. We found that the intergenic region between the genes for the minichromosome maintenance 4 protein (Mcm4) and the catalytic subunit of DNA-dependent protein kinase (Prkdc), whose human counterpart has been identified as a replication origin, contains a number of Myb binding sites. Our data show that this region also acts as an origin of replication in chicken cells. Interestingly, we found that the chicken Mcm4 gene is also Myb-regulated.ConclusionOur work identifies the chicken Mcm4 gene as a novel Myb target gene and presents evidence for the co-localization of two novel origins of DNA replication with Myb-regulated genes. Our work raises the possibility that a fraction of Myb target gene promoters is associated with DNA replication origins.

Highlights

The retroviral oncogene v-myb encodes a transcription factor (v-Myb) which is responsible for the transformation of myelomonocytic cells by avian myeloblastosis virus (AMV). v-Myb is thought to exert its biological effects by deregulating the expression of specific target genes
The oncogene v-myb of avian myeloblastosis virus (AMV) encodes a transcription factor which is responsible for the ability of AMV to transform cells of the myelomonocytic lineage [1,2]. v-myb is derived from the chicken c-myb gene, which plays a crucial role in the development of the hematopoietic system. c-myb is expressed in immature cells of all hematopoietic lineages and is silenced during the terminal differentiation of these cells
Ladenburger et al [22] have previously identified a replication origin located between the human minichromosome maintenance 4 protein (Mcm4) and Prkdc genes

Summary

Introduction

The retroviral oncogene v-myb encodes a transcription factor (v-Myb) which is responsible for the transformation of myelomonocytic cells by avian myeloblastosis virus (AMV). v-Myb is thought to exert its biological effects by deregulating the expression of specific target genes. The retroviral oncogene v-myb encodes a transcription factor (v-Myb) which is responsible for the transformation of myelomonocytic cells by avian myeloblastosis virus (AMV). We have recently demonstrated that the chicken Gas gene, whose promoter co-localizes with an origin of DNA replication, is a bona fide Myb target gene Because of this finding we have asked whether other Myb-regulated genes are associated with DNA replication origins. The oncogene v-myb of avian myeloblastosis virus (AMV) encodes a transcription factor which is responsible for the ability of AMV to transform cells of the myelomonocytic lineage [1,2]. Recent indepth analyses of some Myb target genes, have suggested a more complex picture in which the activation of certain target genes is mediated by cooperation of additional Myb-responsive enhancer elements with the target gene promoters. In case of the chicken C/EBPβ gene Myb targets the promoter as well as an enhancer located downstream of the gene [17]

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