Function of Stem cell Zinc Finger 1 (SZF1) / ZNF589 protein in hematopoietic stem cell survival and differentiation

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The Stem cell Zinc Finger 1 (SZF1)/ZNF589 protein belongs to the large family of KRAB-Zinc Finger transcription factors which epigenetically repress transcription by recruiting chromatin modifying complexes to the promoter region of their target genes. The fact that it was identified as a gene specifically expressed in CD34+ cells, together with the biochemical characteristics of the protein, strongly suggest its implication in epigenetic control of gene expression in hematopoietic stem cells (HSCs). However, the function of SZF1/ZNF589 in hematopoiesis has not yet been studied. My preliminary data support a functional implication of SZF1/ZNF589 in the hematopoietic system. Along with the molecular characterization of SZF1/ZNF589, the aim of this project is to investigate its role in CD34+ cells and to identify its target genes by loss- or gain-of-function studies. The expected results will add new insight into regulatory pathways involved in maintenance, proliferation and differentiation of HSCs, and impact on the understanding of normal and aberrant hematopoiesis.