1. v‐Myb DNA binding is required to block thrombocytic differentiation of Myb‐Ets‐transformed multipotent haematopoietic progenitors.
- Author
-
Frampton, J., McNagny, K., Sieweke, M., Philip, A., Smith, G., and Graf, T.
- Abstract
The E26 avian leukaemia virus encodes a fusion oncoprotein consisting of truncated versions of the c‐Myb and c‐Ets‐1 transcription factors. When used to infect embryonic chicken haematopoietic cells two types of self‐renewing progenitors are obtained, namely myeloblasts and ‘MEPs’ (Myb‐Ets progenitors). In earlier work we have shown that myeloblasts transformed by the ts21 mutant of E26, which has a lesion in v‐Myb, can be induced to differentiate into macrophages following shift to the non‐permissive temperature. Here we show that the ts21 v‐Myb is temperature sensitive for DNA binding in band shift experiments and that its inactivation in transformed MEPs induces their maturation into thrombocytes. The MEP transforming capacity of v‐Myb is not confined to its fusion with v‐Ets, as it is also seen with a virus that co‐expresses tsMyb with v‐ErbB. As with wild‐type E26‐transformed MEPs, ts21‐transformed MEPs are multipotent, differentiating into eosinophils and myeloblasts following treatment with 12‐O‐tetradecanoylphorbol‐13‐acetate. In addition, ts21‐transformed myeloblasts differentiate into macrophages when shifted to the non‐permissive temperature. This shows that v‐Myb blocks haematopoietic differentiation at two distinct stages. In contrast, v‐Ets inactivation in MEPs transformed by a ts E26 mutant with a lesion in the corresponding oncoprotein leads to their differentiation into erythrocytes, myeloblasts and probably eosinophils. These data show that the two domains of Myb‐Ets selectively affect decision making processes in different types and stages of haematopoietic cells.
- Published
- 1995
- Full Text
- View/download PDF