Early hematopoietic zinc finger protein-zinc finger protein 521: a candidate regulator of diverse immature cells.

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.