Myb-induced chromatin remodeling at a dual enhancer/promoter element involves non-coding rna transcription and is disrupted by oncogenic mutations of v-myb.
The oncogene v-myb of avian myeloblastosis virus (AMV) encodes a transcription factor (v-Myb) that transforms myelomonocytic cells by deregulating the expression of specific target genes. v-myb has acquired its oncogenic potential by truncation as well as by a number of point mutations of its cellular progenitor c-myb. As a result of these changes, the target gene spectrum v-Myb differs from that of c-Myb. We recently showed that the chicken mim-1 gene, a c-Myb target gene that is not activated by v-Myb harbors a powerful cell type-specific and Myb-inducible enhancer in addition to a Myb-responsive promoter. We now show that Myb-dependent activation of the mim-1 gene is accompanied by extensive remodeling of the nucleosomal architecture at the enhancer. We found that the mim-1 enhancer region also harbors a promoter whose activity is stimulated by Myb and which directs the transcription of an apparently non-coding RNA. Furthermore, our data show that the oncogenic mutations of AMV have disrupted the ability of v-Myb to induce remodeling of chromatin structure at the mim-1 enhancer. Together, our results demonstrate for the first time directly that Myb induces alterations of the nucleosomal organization at a relevant target site and provide new insight into the functional consequences of the oncogenic amino acid substitutions.
Wilczek
Carola
C
Institut für Biochemie, Westfälische-Wilhelms-Universität Münster, D-48149 Münster, Germany.
Chayka
Olesya
O
Plachetka
Annette
A
Klempnauer
Karl-Heinz
KH
D000123:Acetyltransferases / Q000096:biosynthesis* / Q000235:genetics; D019943:Amino Acid Substitution; D000818:Animals; D009189:Avian Myeloblastosis Virus / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002472:Cell Transformation, Viral / Q000235:genetics; D002645:Chickens; D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D004742:Enhancer Elements, Genetic / Q000502:physiology*; D020570:Genes, myb / Q000235:genetics; D009000:Monocytes / Q000378:metabolism*; D009154:Mutation; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism; D020626:Oncogene Proteins v-myb / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000502:physiology*; D022661:RNA, Untranslated / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology
D009707:Nucleosomes; D020626:Oncogene Proteins v-myb; D022661:RNA, Untranslated; D000123:Acetyltransferases; C077509:mim-1 protein, Gallus gallus