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The human  ZNF268  gene encodes a typical KRAB-C2H2 zinc finger protein that may participate in hematopoiesis and leukemogenesis. A recent microarray study revealed that  ZNF268  expression continuously decreases during erythropoiesis. However, the molecular mechanisms underlying regulation of  ZNF268  during hematopoiesis are not well understood. Here we found that GATA-1, a master regulator of erythropoiesis, repressed the promoter activity and transcription of  ZNF268 . Electrophoretic mobility shift assays and chromatin immunoprecipitation assays showed that GATA-1 directly bound to a GATA binding site in the  ZNF268  promoter  in vitro  and  in vivo . Knockdown of  ZNF268  in K562 erythroleukemia cells with specific siRNA accelerated cellular proliferation, suppressed apoptosis, and reduced expression of erythroid-specific developmental markers. It also promoted growth of subcutaneous K562-derived tumors in nude mice. These results suggest that  ZNF268  is a crucial downstream target and effector of GATA-1. They also suggest the downregulation of  ZNF268  by GATA-1 is important in promoting the growth and suppressing the differentiation of K562 erythroleukemia cells.

Knockdown of ZNF268, which Is Transcriptionally Downregulated by GATA-1, Promotes Proliferation of K562 Cells