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Histone deacetylases (HDACs) are a growing family of enzymes implicated in transcriptional regulation by affecting the acetylation state of core histones in the nucleus of cells. HDACs are known to have key roles in the regulation of cell proliferation [Brehm, Miska, McCance, Reid, Bannister and Kouzarides (1998) Nature (London) 391, 597-600], and aberrant recruitment of an HDAC complex has been shown to be a key step in the mechanism of cell transformation in acute promyelocytic leukaemia [Grignani, De Matteis, Nervi, Tomassoni, Gelmetti, Cioce, Fanelli, Ruthardt, Ferrara, Zamir et al. (1998) Nature (London) 391, 815-818; Lin, Nagy, Inoue, Shao, Miller and Evans (1998), Nature (London) 391, 811-814]. Here we present the complete nucleotide sequence of a cDNA clone, termed HDAC8, that encodes a protein product with similarity to the RPD3 class (I) of HDACs. The predicted 377-residue HDAC8 product contains a shorter C-terminal extension relative to other members of its class. After expression in two cell systems, immunopurified HDAC8 is shown to possess trichostatin A- and sodium butyrate-inhibitable HDAC activity on histone H4 peptide substrates as well as on core histones. Expression profiling reveals the expression of HDAC8 to various degrees in every tissue tested and also in several tumour lines. Mutation of two adjacent histidine residues within the predicted active site severely decreases activity, confirming these residues as important for HDAC8 enzyme activity. Finally, linkage analysis after radiation hybrid mapping has localized HDAC8 to chromosomal position Xq21.2-Xq21.3. These results confirm HDAC8 as a new member of the HDAC family.

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A great deal of new knowledge and research material has been generated from research carried out under the auspices of the EU. However, only a small amount has been made available as practical policysupport tools. In this paper we describe how EU funded research models and understanding has been integrated into an interactive Decision Support System addressing physical, economic and social aspects of land degradation in the Mediterranean. We summarise the 10 constituent models that simulate hydrology, human influences, crops, natural vegetation and climatic conditions. The models operate on very different spatial and temporal scales and utilise different modelling techniques and implementation languages. Many scientific, modelling and technical issues were encountered during the transformation of 'research' models into 'policy' models. We highlight the differences between each type of model and discuss some of the ontological and technical problems in re-using research models for policy-support, including resolving differences in temporal scale and some of the software engineering aspects of model integration. The involvement of policy-makers, 'stakeholders' and other end-users is essential for the specification of relevant decision-making issues and the development of useful interactive support tools. We discuss the problems of identifying both the decision-makers and the issues they perceive as important, their receptivity to such tools, and their roles in the policy-making process. Finally, we note the lessons learned, the resources needed, and the types of end-users, scientists and mediators required to ensure effective communication, technical development and exploitation of spatial modelling tools for integrated environmental decision-making.