Two disparate topics will be presented.
1. Silencing of Retrovirus Expression in Embryonic Stem (ES) Cells It has long been known that ES cells potently block provirus expression via a trans-acting factor that binds to the primer binding site (PBS) for proline tRNA on the murine leukemia virus genome. We purified the silencing complex and identified TRIM28 (Kap-1), a known transcriptional silencer, as an integral component of the complex. Further, we have identified the DNA sequence-specific binding component of the complex as being ZFP809, one of the dozens of zinc finger proteins encoded in the mammalian genome. We show that expression of ZFP809 is sufficient to render even differentiated cells highly resistant to MLV infection. We found that similar silencing occurs at the distinct PBS for at least one other tRNA (namely, Lys1,2) utilized by such viruses as visna and spuma. The protein complex that mediates this silencing is large: at least two more components have been implicated, HP1gamma and EBP-1, and more are likely to be found. We have also begun characterizing a non-PBS directed silencing complex acting more broadly on incoming DNAs in ES cells.

2. A New Retroelement in the Mollusc Mya arenaria Over the past thirty years the soft-shell clam has been subject to a neoplastic disease of rapidly increasing prevalence, variously known as “disseminated neoplasia” (DN) or “haemic neoplasia” (HN). The beds in many locations in the Northeast Atlantic have been decimated by the disease, and the incidence in affected areas can range from 10% to as high as 900f the animals. The disease is similar in many ways to mammalian leukemia, with a huge expansion of blast-like cells in the hemolymph with high mitotic index. The etiology of the disease is mysterious; suggestions have included both environmental pollution and infectious agents. We have discovered that the hemolymph of the diseased animals often contain high levels of extracellular reverse transcriptase. Deep sequencing of RNA preparations from cell-free hemolymph has revealed a novel retroelement with sequence similarity to those of the mammalian retroviruses. We will report our progress in characterizing the element.

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