Early hematopoietic zinc finger protein—zinc finger protein 521: A candidate regulator of diverse immature cells

Laboratory of Molecular Haematopoiesis, Department of Experimental and Clinical Medicine, University of Catanzaro Magna Graecia, 88100 Catanzaro, Italy.
The International Journal of Biochemistry & Cell Biology (Impact Factor: 4.05). 02/2008; 40(5):848-54. DOI: 10.1016/j.biocel.2007.04.006
Source: PubMed


The early hematopoietic zinc finger protein/zinc finger protein 521 (EHZF/ZNF521) is a recently identified, 1131 amino-acid-long nuclear factor that contains 30 zinc fingers distributed in clusters throughout its sequence. A 13-AA motif, that binds to components of the nuclear remodelling and histone deacetylation (NuRD) complex and is conserved in several trascriptional co-repressors, is located at the amino-terminal end of the molecule. EHZF/ZNF521 expression is high in the most immature cells of the haematopoietic system and declines with differentiation. Its transcript is also abundant in brain, particularly in the cerebellum. Its murine counterpart, Evi3/Zfp521, is enriched in haematopoietic and neural stem cells, in cerebellar granule neuron precursors and in the developing striatum. Enforced expression of EHZF/ZNF521 in haematopoietic progenitors results in their expansion and in inhibition of differentiation. EHZF/ZNF521 is a member of the BMP signalling pathway and an inhibitor of the transcription factor OLF1/EBF1, implicated in the differentiation of neural progenitors and in the specification of the B-cell lineage. EHZF expression is observed in most acute myelogenous leukaemias and is particularly high in those with rearrangements of the MLL gene, where EHZF may contribute to the leukaemic phenotype. EHZF/ZNF521 is also abundant in medulloblastomas and other brain tumours. Taken together, the data available suggest a possible role for this factor in development, stem cell regulation and oncogenesis.

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    • "Mediators of Inflammation partially known, we have investigated the expression of a group of zinc finger proteins potentially implicated in the physiological regulation of the homeostasis of articular chondrocytes , namely, ZNF423, ZNF470, ZNF521, and ZNF780B. ZNF521/EHZF is a large multifunctional protein with 30 zinc fingers, identified in our laboratory for its selective abundance in immature hematopoietic progenitors compared to mature leukocytes [5] [6]. ZNF521 shows features of a transcriptional corepressor and has been found to modulate the transcriptional induction of erythroid and B-lymphoid differentiation by GATA1 and EBF1 [7] [8]. "
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    ABSTRACT: Articular chondrocytes are responsible for the maintenance of healthy articulations; indeed, dysregulation of their functions, including the production of matrix proteins and matrix-remodeling proteases, may result in fraying of the tissue and development of osteoarthritis (OA). To explore transcriptional mechanisms that contribute to the regulation of chondrocyte homeostasis and may be implicated in OA development, we compared the gene expression profile of a set of zinc finger proteins potentially linked to the control of chondrocyte differentiation and/or functions (ZNF423, ZNF470, ZNF521, and ZNF780B) in chondrocytes from patients affected by OA and from subjects not affected by OA. This analysis highlighted a significantly lower expression of the transcript encoding ZNF423 in chondrocytes from OA, particularly in elderly patients. Interestingly, this decrease was mirrored by the similarly reduced expression of PPARγ, a known target of ZNF423 with anti-inflammatory and chondroprotective properties. The ZNF521 mRNA instead was abundant in all primary chondrocytes studied; the RNAi-mediated silencing of this gene significantly altered the COL2A/COL1 expression ratio, associated with the maintenance of the differentiated phenotype, in chondrocytes cultivated in alginate beads. These results suggest a role for ZNF423 and ZNF521 in the regulation of chondrocyte homeostasis and warrant further investigations to elucidate their mechanism of action.
    Full-text · Article · May 2014 · Mediators of Inflammation
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    • "In the hematopoietic system, its human counterpart ZNF521 binds and inhibits GATA-1 via ZF21 to ZF26, and this maintains the stemness of hematopoietic progenitors and represses erythroid differentiation [8]. Depletion of ZNF521 by shRNA can transform K562 and HEL cells into erythroid cells synthesizing hemoglobin and glycophorin A. The C-terminus of ZNF521 is also required for interaction/inhibition of OLF1/EBF1, and the latter is important for activating B-cell-specific gene expression [9] and for the development of striatal medium spiny neurons [10]. Zfp521 also associates and attenuates RunX2 via ZF6 to ZF26 [11,12], and regulates two stages of osteoblast development during mesenchymal cell lineage commitment and during osteoblast maturation [12,13]. "
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    ABSTRACT: Neural induction is largely considered a default process, whereas little is known about intrinsic factors that drive neural differentiation. Kamiya and colleagues now demonstrate that a transcription factor, Zfp521, is capable of directing embryonic stem (ES) cells into neural progenitors. They discovered that Zfp521 transcripts were enriched in early neural lineage of ES cell differentiation. Forced expression of Zfp521 turned ES cells into neural progenitors in culture conditions that would normally inhibit neural differentiation. Zfp521 was expressed in mouse embryos during gastrulation. The protein was shown to associate with a co-activator p300 and directly induce expression of early neural genes. Knockdown of the Zfp521 by shRNA halted cells at the epiblast stage and suppressed neural differentiation. Zfp521 is a nuclear protein with 30 Krüppel-like zinc fingers mediating multiple protein-protein interactions, and regulates transcription in diverse tissues and organs. The protein promotes proliferation, delays differentiation and reduces apoptosis. The findings by Kamiya and colleagues that Zfp521 directs and sustains early neural differentiation now opens up a series of studies to investigate roles of Zfp521 in stem cells and brain development of mice and men.
    Full-text · Article · Apr 2011 · Stem Cell Research & Therapy
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    • "ZNF521, in humans is known to regulate ontogenesis of the hemato-vascular system through BMP pathways. OAZ/ZNF423 can also repress BMPs by activating repressors of BMPs [87,88]. OAZ can apparently use different clusters of zinc fingers to interact with DNA, RNA or Protein [89]. "
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    ABSTRACT: A recent comparative genomic analysis tentatively identified roughly 40 orthologous groups of C2H2 Zinc-finger proteins that are well conserved in "bilaterians" (i.e. worms, flies, and humans). Here we extend that analysis to include a second arthropod genome from the crustacean, Daphnia pulex. Most of the 40 orthologous groups of C2H2 zinc-finger proteins are represented by just one or two proteins within each of the previously surveyed species. Likewise, Daphnia were found to possess a similar number of orthologs for all of these small orthology groups. In contrast, the number of Sp/KLF homologs tends to be greater and to vary between species. Like the corresponding mammalian Sp/KLF proteins, most of the Drosophila and Daphnia homologs can be placed into one of three sub-groups: Class I-III. Daphnia were found to have three Class I proteins that roughly correspond to their Drosophila counterparts, dSP1, btd, CG5669, and three Class II proteins that roughly correspond to Luna, CG12029, CG9895. However, Daphnia have four additional KLF-Class II proteins that are most similar to the vertebrate KLF1/2/4 proteins, a subset not found in Drosophila. Two of these four proteins are encoded by genes linked in tandem. Daphnia also have three KLF-Class III members, one more than Drosophila. One of these is a likely Bteb2 homolog, while the other two correspond to Cabot and KLF13, a vertebrate homolog of Cabot. Consistent with their likely roles as fundamental determinants of bilaterian form and function, most of the 40 groups of C2H2 zinc-finger proteins are conserved in kind and number in Daphnia. However, the KLF family includes several additional genes that are most similar to genes present in vertebrates but missing in Drosophila.
    Full-text · Article · Apr 2010 · BMC Genomics
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