Cellular functions of the transposon-derived domesticated SETMAR gene in human cells

• Applicant: Dr. Zsuzsanna Izsvak
• Subject Area: Cell Biology
• Term: from 2008 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 62257069

Transposons are molecular parasites that propagate themselves using resources of the host cell. Despite their parasitic nature, there is increasing evidence that transposable elements are a powerful force in gene evolution. For example, transposon sequences can become parts of host genes, and thereafter fulfill functions for the host. However, the cellular functions of these “domesticated”, transposon-derived genes are largely unknown. A transposase coding region got fused to a histone methyltransferase gene ~50 million years ago in a common ancestor of anthropoid primates. This chimeric gene, called SETMAR, is expressed throughout the human body, and positive selection has been preserving its coding sequence in all anthropoid lineages. SETMAR exhibits histone methyltransferase as well as transposon DNA binding and nicking activities in vitro. The physiological function of SETMAR remains an enigma. We propose hypothesis-driven research that presumes that the SETMAR protein and its ≈1500 binding sites dispersed in the human genome constitute a primate-specific gene regulatory network. We consider two major lines of research addressing a role of SETMAR in gene regulation through locus-specific chromatin modifications and/or by regulating the function of transposon-derived human microRNAs. The proposed research could provide insights into the mechanisms and roles of transposable elements in human evolution.

• DFG Programme: Research Grants