promyelocytes there is an increase in the amount of p85 subunit protein whereas the level of the p75 subunit is unchanged. In differentiating mouse G8 myoblasts there is, however, an upregulation of both the p75 and p85 subunits and of the p85 mRNA. An inhibition of mouse myoblast differentiation by either cAMP, 3-aminobenzamide or sodium butyrate abolishes the upregulation of the p85 subunit. In G8 myoblasts chemical, or physical stress by UV fight or X-rays does not upregulate the level of the p85 subunit. The possible involvement of NHP1 in the active demethylation of bifilarly methylated DNA will be discussed.

Thrombomodulin (TM) is expressed on vascular endothelial cells and plays an important role in the anticoagulant pathway by maintaining the thrombo-resistance of the blood vessel wall. We show that in primary human endothelial cells TM gene expression is repressed at the transcriptional level by Tumour necrosis factor (TNF alpha) through a protein kinase C independent pathway. The TM promoter is highly active in endothelial cells and is inhibited by TNF alpha. The -76/-56 region mediates both specific high basal activity and TNF alpha-repression. It binds a nuclear factor specific to endothelial cells, that appears to belong to the Ets-family by various criteria. The -76/-56 region contains three direct repeats of the ets-core sequence GGAA that are important for specific high basal activity, TNF alpha repression and trans-activation by expression of Ets-1 and 2. Although human Ets-1 (h-Ets-1) and chicken c-Ets-1 and 2 stimulate the TM promoter through the -76/-56 element, their activity is not suppressed by TNF alpha. c-Ets-1 competes and overrides TNF alpha repression in a concentration dependent manner. We propose that either a different member of the Ets domain protein family, or an Ets-associated co-factor, is the target of the TNF alpha signalling cascade in endothelial cells.