The stem cell zinc finger 1 (SZF1)/ZNF589 protein belongs to the large family of 
Krüppel-associated box domain-zinc finger (KRAB-ZNF) transcription factors, 
which are present only in higher vertebrates and epigenetically repress 
transcription by recruiting chromatin-modifying complexes to the promoter 
regions of their respective target genes. Although the distinct biological 
functions of most KRAB-ZNF proteins remain unknown, recent publications indicate 
their implication in fundamental processes, such as cell proliferation, 
apoptosis, differentiation, development, and tumorigenesis. SZF1/ZNF589 was 
first identified as a gene with SZF1-1 isoform specifically expressed in CD34(+) 
hematopoietic cells, strongly suggesting a role in epigenetic control of gene 
expression in hematopoietic stem/progenitor cells (HSPCs). However, the function 
of SZF1/ZNF589 in hematopoiesis has not yet been elucidated. Our study reveals 
SZF1/ZNF589 as a gene with a human-specific nucleotide DNA-change, conferring 
potential species-specific functional properties. Through shRNA-mediated 
loss-of-function experiments, we found that changes in expression of fundamental 
apoptosis-controlling genes are induced on SZF1/ZNF589 knockdown, resulting in 
inhibited growth of hematopoietic cell lines and decreased progenitor potential 
of primary human bone marrow CD34(+) cells. Moreover, we found that the 
SZF1/ZNF589 gene is differentially regulated during hypoxia in CD34(+) HSPCs in 
a cytokine-dependent manner, implicating its possible involvement in the 
maintenance of the hypoxic physiologic status of hematopoietic stem cells. Our 
results establish the role of SZF1/ZNF589 as a new functional regulator of the 
hematopoietic system.