c-Myb protein binds to the EP element of the HBV enhancer and regulates transcription in synergy with NF-M.
The hepatitis B virus (HBV) enhancer contains multiple active elements, one of which is the EP element, a 15 bp site important for its regulation by acting on other functional elements like the E site. The EP element, in the HBV enhancer context, contains two putative binding sites for c-myb family gene products. Electrophoretic mobility shift assays showed that the minimal c-Myb DNA-binding domain binds to the EP sequence. DNase I footprinting experiments revealed that only one consensus binding site was effectively protected. We found that c-Myb down-regulates transcription driving by the HBV enhancer in CAT assays performed in a haematopoietic (K562) and in a hepatic (HepG2) cell line. Interestingly, co-expression of both c-Myb and NF-M, a C/EBPbeta homologue which recognises the E element of the HBV enhancer, showed a synergistic transactivation of the HBV enhancer while, separately, each of them had an inhibitory effect on transcription in HepG2 and K562 cell lines, two cell types potentially infected by the hepatitis B virus.
U 124 INSERM Onco-Hématologie Moléculaire, Institut de Recherches sur le Cancer de Lille, Place de Verdun, 59.045, Lille, France.
M H
MH
David-Cordonnier
M
M
Hamdane
J C
JC
D'Halluin
D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins; D002460:Cell Line; D018983:DNA Footprinting; D015536:Down-Regulation; D004742:Enhancer Elements, Genetic; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020598:Proto-Oncogene Proteins c-myb; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
C083058:C-EPB transcription factor; D022762:CCAAT-Enhancer-Binding Proteins; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D015534:Trans-Activators; D014157:Transcription Factors