title: Zinc finger protein 521 antagonizes early B-cell factor 1 and modulates the B-lymphoid differentiation of primary hematopoietic progenitors.
abstract: Zinc finger protein 521 (EHZF/ZNF521) is a multi-functional transcription co-factor containing 30 zinc fingers and an amino-terminal motif that binds to the nucleosome remodelling and histone deacetylase (NuRD) complex. ZNF521 is believed to be a relevant player in the regulation of the homeostasis of the hematopoietic stem/progenitor cell compartment, however the underlying molecular mechanisms are still largely unknown. Here, we show that this protein plays an important role in the control of B-cell development by inhibiting the activity of early B-cell factor-1 (EBF1), a master factor in B-lineage specification. In particular, our data demonstrate that: (1) ZNF521 binds to EBF1 via its carboxyl-terminal portion and this interaction is required for EBF1 inhibition; (2) NuRD complex recruitment by ZNF521 is not essential for the inhibition of transactivation of EBF1-dependent promoters; (3) ZNF521 represses EBF1 target genes in a human B-lymphoid molecular context; and (4) RNAi-mediated silencing of ZNF521/Zfp521 in primary human and murine hematopoietic progenitors strongly enhances the generation of B-lymphocytes in vitro. Taken together, our data indicate that ZNF521 can antagonize B-cell development and lend support to the notion that it may contribute to conserve the multipotency of primitive lympho-myeloid progenitors by preventing or delaying their EBF1-driven commitment toward the B-cell lineage.
authors: Laboratory of Molecular Hematopoiesis, University of Catanzaro Magna Græcia, Catanzaro, Italy.
authors: Tiziana
authors: T
authors: Mega
authors: Michela
authors: M
authors: Lupia
authors: Nicola
authors: N
authors: Amodio
authors: Sarah J
authors: SJ
authors: Horton
authors: Maria
authors: M
authors: Mesuraca
authors: Daniela
authors: D
authors: Pelaggi
authors: Valter
authors: V
authors: Agosti
authors: Michele
authors: M
authors: Grieco
authors: Emanuela
authors: E
authors: Chiarella
authors: Raffaella
authors: R
authors: Spina
authors: Malcolm A S
authors: MA
authors: Moore
authors: Jan Jacob
authors: JJ
authors: Schuringa
authors: Heather M
authors: HM
authors: Bond
authors: Giovanni
authors: G
authors: Morrone