title: Knockdown of ZNF268, which is transcriptionally downregulated by GATA-1, promotes proliferation of K562 cells.
abstract: 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.
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zeng
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Ma
authors.forename: Xianguo
authors.initials: X
authors.lastname: Wang
authors.forename: Mingxiong
authors.initials: M
authors.lastname: Guo
authors.forename: Wenxin
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001665:Binding Sites; D014408:Biomarkers, Tumor / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics*; D041905:Erythroid Cells / Q000378:metabolism; D050982:GATA1 Transcription Factor / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D020014:K562 Cells; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011401:Promoter Regions, Genetic / Q000235:genetics; D012097:Repressor Proteins / Q000172:deficiency* / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D050982:GATA1 Transcription Factor; D012097:Repressor Proteins; C482295:ZNF268 protein, human