PMID- 24180487
OWN - NLM
STAT- MEDLINE
DCOM- 20140414
LR  - 20140120
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 458
IP  - 1
DP  - 2014 Feb 15
TI  - ZNF16 (HZF1) promotes erythropoiesis and megakaryocytopoiesis via regulation of 
      the c-KIT gene.
PG  - 171-83
LID - 10.1042/BJ20130628 [doi]
AB  - We previously characterized the zinc finger protein gene HZF1 [also known as 
      ZNF16 (zinc finger protein 16)] and demonstrated its important roles in erythroid 
      and megakaryocytic differentiation of K562 cells. In the present study, we 
      investigated its effect on erythroid and megakaryocytic differentiation of HSPCs 
      (haemopoietic stem/progenitor cells). We observed up-regulation of ZNF16 during 
      erythroid and megakaryocytic differentiation of the CD34+ HSPCs, and demonstrated 
      that ZNF16 promotes erythroid and megakaryocytic differentiation by 
      gain-of-function and loss-of-function experiments. Using a luciferase reporter 
      and ChIP assays ZNF16 was demonstrated to bind to the c-KIT gene promoter and 
      inhibit its expression in K562 cells. Enforced expression and knockdown of ZNF16 
      down-regulated and up-regulated the expression of the c-KIT gene in K562 cells 
      and HSPCs respectively. Significantly decreased levels of the c-Kit protein were 
      observed following erythroid and megakaryocytic differentiation of K562 and CD34+ 
      cells. The knockdown of c-KIT partially rescued the differentiation inhibition 
      caused by ZNF16 knockdown. The knockdown of c-KIT also blocked the activity of 
      the c-Raf/MEK [MAPK (mitogen-activated protein kinase)/ERK 
      (extracellular-signal-regulated kinase) kinase]/ERK/c-Jun signal pathway and 
      reduced further the level of HEY1 (hes-related family bHLH transcription factor 
      with YRPW motif 1), a repressor of GATA1 (GATA-binding protein 1) transcription, 
      which finally up-regulated the expression of GATA1, a central regulator of 
      erythroid and megakaryocytic differentiation. In conclusion the results of the 
      present study demonstrate that ZNF16 plays an important role in erythropoiesis 
      and megakaryocytopoiesis via its regulation of the 
      c-Kit/c-Raf/MEK/ERK/c-Jun/HEY1/GATA1 cascade.
FAU - Chen, Jing
AU  - Chen J
AD  - *Key State Laboratory of Medical Molecular Biology, Department of Biochemistry 
      and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of 
      Medical Sciences and Peking Union Medical College, Beijing, 100005, China.
FAU - Li, Xiao-Bo
AU  - Li XB
AD  - *Key State Laboratory of Medical Molecular Biology, Department of Biochemistry 
      and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of 
      Medical Sciences and Peking Union Medical College, Beijing, 100005, China.
FAU - Su, Rui
AU  - Su R
AD  - *Key State Laboratory of Medical Molecular Biology, Department of Biochemistry 
      and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of 
      Medical Sciences and Peking Union Medical College, Beijing, 100005, China.
FAU - Song, Li
AU  - Song L
AD  - *Key State Laboratory of Medical Molecular Biology, Department of Biochemistry 
      and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of 
      Medical Sciences and Peking Union Medical College, Beijing, 100005, China.
FAU - Wang, Fang
AU  - Wang F
AD  - *Key State Laboratory of Medical Molecular Biology, Department of Biochemistry 
      and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of 
      Medical Sciences and Peking Union Medical College, Beijing, 100005, China.
FAU - Zhang, Jun-Wu
AU  - Zhang JW
AD  - *Key State Laboratory of Medical Molecular Biology, Department of Biochemistry 
      and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of 
      Medical Sciences and Peking Union Medical College, Beijing, 100005, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (DNA Primers)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (ZNF266 protein, human)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Base Sequence
MH  - Cell Differentiation/drug effects
MH  - Cell Line, Tumor
MH  - DNA Primers
MH  - DNA-Binding Proteins/*physiology
MH  - Erythropoiesis/*physiology
MH  - Gene Expression Regulation/*physiology
MH  - Humans
MH  - K562 Cells
MH  - Megakaryocytes/*cytology
MH  - Proto-Oncogene Proteins c-kit/*genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Tetradecanoylphorbol Acetate/pharmacology
EDAT- 2013/11/05 06:00
MHDA- 2014/04/15 06:00
CRDT- 2013/11/05 06:00
PHST- 2013/11/05 06:00 [entrez]
PHST- 2013/11/05 06:00 [pubmed]
PHST- 2014/04/15 06:00 [medline]
AID - BJ20130628 [pii]
AID - 10.1042/BJ20130628 [doi]
PST - ppublish
SO  - Biochem J. 2014 Feb 15;458(1):171-83. doi: 10.1042/BJ20130628.