1: Mol Cell Biol. 1995 Nov;15(11):6075-87. 

Overexpression of the zinc finger protein MZF1 inhibits hematopoietic
development from embryonic stem cells: correlation with negative regulation of
CD34 and c-myb promoter activity.

Perrotti D, Melotti P, Skorski T, Casella I, Peschle C, Calabretta B.

Department of Microbiology and Immunology, Jefferson Cancer Institute, Thomas
Jefferson University, Philadelphia, Pennsylvania 19107, USA.

Zinc finger genes encode proteins that act as transcription factors. The myeloid
zinc finger 1 (MZF1) gene encodes a zinc finger protein with two DNA-binding
domains that recognize two distinct consensus sequences, is preferentially
expressed in hematopoietic cells, and may be involved in the transcriptional
regulation of hematopoiesis-specific genes. Reverse transcription-PCR analysis
of human peripheral blood CD34+ cells cultured under lineage-restricted
conditions demonstrated MZF1 expression during both myeloid and erythroid
differentiation. Sequence analysis of the 5'-flanking region of the CD34 and
c-myb genes, which are a marker of and a transcriptional factor required for
hematopoietic proliferation and differentiation, respectively, revealed closely
spaced MZF1 consensus binding sites found by electrophoretic mobility shift
assays to interact with recombinant MZF1 protein. Transient or constitutive MZF1
expression in different cell types resulted in specific inhibition of
chloramphenicol acetyltransferase activity driven by the CD34 or c-myb
5'-flanking region. To determine whether transcriptional modulation by MZF1
activity plays a role in hematopoietic differentiation, constructs containing
the MZF1 cDNA under the control of different promoters were transfected into
murine embryonic stem cells which, under defined in vitro culture conditions,
generate colonies of multiple hematopoietic lineages. Constitutive MZF1
expression interfered with the ability of embryonic stem cells to undergo
hematopoietic commitment and erythromyeloid colony formation and prevented the
induced expression of CD34 and c-myb mRNAs during differentiation of these
cells. These data indicate that MZF1 plays a critical role in hematopoiesis by
modulating the expression of genes involved in this process.

PMID: 7565760 [PubMed - indexed for MEDLINE]


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