Negative transcriptional regulatory mechanisms of cytokine LD78 which regulates hematopoiesis

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From several lines of evidence, it seems likely that a silencer element inhibits chemokine LD78 gene expression in the cells where no message is found. We have tried to identify and purify the transcriptional regulators which bind to this silencer element and to the ICK-1 element. The ICK-1 element is present in the promoter and regulates the LD78 transcription positively and negatively. However, These transcriptional regulators are very unstable and therefore it was difficult to purify them. We also analyzed the promoter of a chemokine family member MCP-3. MCP-3 promoter was active in HeLa cells, although no MCP-3 message was found. Since chomkines genes are clustered on human chromosome 17, the silencer element which inhibits the LD78 expression may also repress the expression of MCP-3 and other chemokine genes. We therefore constructed a yeast artificial chromosome (YAC) contig of several Mb long containing all chemokine genes present on chromosome 17q11.2. The contig also contains four chemokine-like genes which were deposited in GenBank as ESTs. This YAC contig is useful for identification of new chemokine genes in addition to the analysis of the silencer element.