Research article

Selective inhibition of c-Myb DNA-binding by RNA polymers

Oddmund Nordgård^1,2 , Tor Ø Andersen¹ and Odd S Gabrielsen¹

¹Department of Molecular Biosciences, University of Oslo, P.O.Box 1041 Blindern, N-0316 Oslo, Norway

²Department of Haematology and Oncology, Rogaland Central Hospital, P.O.Box 8100, N-4068 Stavanger, Norway

author email corresponding author email

BMC Biochemistry 2004, 5:15doi:10.1186/1471-2091-5-15

Published:	4 November 2004

Abstract

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.

Conclusion

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.