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Series GSE46593 Query DataSets for GSE46593
Status Public on Mar 29, 2016
Title Analysis of the effects of ZNF16 on gene expression in k562 cells.
Organism Homo sapiens
Experiment type Expression profiling by array
Summary We previously characterized zinc finger protein gene HZF1 (ZNF16) and demonstrated its important roles in erythroid and megakaryocytic differentiation of K562 cells by loss-function assay. However its effect in erythroid and megakaryocytic differentiation of hematopoietic stem/progenitor cells (HSPCs) and the mechanisms by which it functions have not been understood. In this study, we detected up-regulation of ZNF16 during erythroid and megakaryocytic differentiation of K562 cells and normal CD34+ HSPCs, and demonstrated that ZNF16 promotes erythroid and megakaryocytic differentiation by gain-of-function and loss-of-function experiments. Gene expression profiling by mRNA array and PCR validation in the K562 transforments with ZNF16 over-expression suggested that cell division cycle-associated 7-like gene (JPO2) and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog gene (c-KIT) were among the genes regulated possibly by ZNF16. Luciferase reporter assay and Chromatin Immunoprecipitation demonstrated that ZNF16 binds to JPO2 and c-KIT promoters and inhibits their expression in K562 cells. A significant decrease of JPO2 and c-KIT levels was observed during erythroid and megakaryocytic differentiation of K562 and CD34+ cells. The knockdown of either JPO2 or c-KIT partially rescued the differentiation inhibition caused by ZNF16 knockdown. We also found that ZNF16 inhibits c-KIT/c-Raf/MEK/ERK/c-Jun/HEY1 signal pathways, which finally up-regulated expression of GATA1, a central regulator of erthroid and megakaryocyte differentiation. By lentivirus-mediated gene transfer, we demonstrated that enforced expression and knockdown of ZNF16 in HSPCs down-regulated and up-regulated expression of its targets respectively. Our data collectively demonstrate that ZNF16 promotes erythropoiesis and megakaryocytopoiesis via its regulation on JPO2 and c-KIT.
 
Overall design 4 samples are analyzed, H4-1 and H4-2 are two stable K562 transductants with ZNF16 over-expression, PC1 and PC2 are stable control K562 transductants. Stable K562 transductants were obtained for RNA extraction and hybridization on an Illumina HumanHT-12 V4.0 expression beadchipe xpression Array platform.
 
Contributor(s) Chen J, Zhang J
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Submission date May 02, 2013
Last update date Mar 29, 2016
Contact name Junwu Zhang
E-mail(s) zhangjunwupumc@sina.cn
Organization name National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences,
Street address 5 Dong Dan San Tiao
City Bei Jing
ZIP/Postal code 100005
Country China
 
Platforms (1)
GPL10904 Illumina HumanHT-12 V4.0 expression beadchip (gene symbol)
Samples (4)
GSM1132996 Stable K562 transductants _ ZNF16 over-expression_rep1
GSM1132997 Stable K562 transductants _ ZNF16 over-expression_rep2
GSM1132998 Stable K562 transductants_ control_ rep1
Relations
BioProject PRJNA201064

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE46593_non_normalized.txt.gz 1.0 Mb (ftp)(http) TXT
Processed data included within Sample table

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