Characterization of a novel zinc finger gene with increased expression in nondividing normal human cells

We report here the cloning and characterization of a novel KRAB zinc finger gene, ZFQR, which has eight tandemly repeated zinc fingers, a complete KRA B box at the N-terminal region, and a unique C-terminal sequence. It is exp ressed in a variety of human tissues, and mRNA levels are upregulated in no ndividing senescent and quiescent human fibroblasts. Overexpression of the protein in quiescent cells stimulated with serum growth factors results in inhibition of entry into the cell cycle. The latter activity is lost when t he N-terminal KRAB domain is deleted. The KRAB domain is also required for the transcriptional repression activity of ZFQR and in maintaining associat ion of the protein with the nuclear matrix. The gene has been mapped to hum an chromosome 19q13.4. The association of ZFQR with the nuclear matrix, tra nscriptional repression activity, increased expression in senescent and qui escent cells, and the ability to inhibit quiescent cells stimulated with gr owth factors from entering the cell cycle suggests a role for ZFQR in the m aintenance of the nondividing state of normal human cells. (C) 2001 Academi c Press.