Selective inhibition of c-Myb DNA-binding by RNA polymers.
BACKGROUND
The transcription factor c-Myb is expressed in hematopoietic progenitor cells and other rapidly proliferating tissues, regulating genes important for proliferation, differentiation and survival. The DNA-binding domain (DBD) of c-Myb contains three tandemly arranged imperfect repeats, designated Myb domain R1, R2 and R3. The three-dimensional structure of the DBD shows that only the second and third Myb domains are directly involved in sequence-specific DNA-binding, while the R1 repeat does not contact DNA and only marginally affects DNA-binding properties. No structural information is available on the N-terminal 30 residues. Since deletion of the N-terminal region including R1 plays an important role in oncogenic activation of c-Myb, we asked whether this region confers properties beyond DNA-binding to the neighbouring c-Myb DBD.


RESULTS
Analysis of a putative RNA-binding function of c-Myb DBD revealed that poly(G) preferentially inhibited c-Myb DNA-binding. A strong sequence-selectivity was observed when different RNA polymers were compared. Most interesting, the poly(G) sensitivity was significantly larger for a protein containing the N-terminus and the R1-repeat than for the minimal DNA-binding domain.


CONCLUSIONS
Preferential inhibition of c-Myb DNA binding by poly(G) RNA suggests that c-Myb is able to interact with RNA in a sequence-selective manner. While R2 and R3, but not R1, are necessary for DNA-binding, R1 seems to have a distinct role in enhancing the RNA-sensitivity of c-Myb.
Nordgård
Oddmund
O
Department of Molecular Biosciences, University of Oslo, Norway. nood@ext.sir.no <nood@ext.sir.no>
Andersen
Tor Ø
TØ
Gabrielsen
Odd S
OS
D004247:DNA / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D011068:Poly G / Q000378:metabolism; D011108:Polymers / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism*; D012313:RNA / Q000378:metabolism
D011108:Polymers; D020598:Proto-Oncogene Proteins c-myb; D011068:Poly G; D012313:RNA; D004247:DNA