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 b site important for its regulation by ac ting on other functional elements like the E site. The EP element, in the H BV enhancer context, contains two putative binding sites for c-myb family g ene products. Electrophoretic mobility shift assays showed that the minimal c-Myb DNA-binding domain binds to the EP sequence. DNase I footprinting ex periments revealed that only one consensus binding site was effectively pro tected. We found that c-Myb down-regulates transcription driving by the HBV enhancer in CAT assays performed ina haematopoietic (K562) and in a hepati c (HepG2) cell line. Interestingly,coexpression of both c-Myb and NF-M, a C /EBP beta homologue which recognises the E element of the HBV enhancer, sho wed a synergistic transactivation of the HBV enhancer while, separately, ea ch of them had an inhibitory effect on transcription ill HepG2 and K562 cel l lines, two cell types potentially infected by the hepatitis B virus. (C) 1999 Elsevier Science B.V. All rights reserved.