Zinc finger protein 521 antagonizes early B-cell factor 1 and modulates the B-lymphoid differentiation of primary hematopoietic progenitors Journal Article
| Authors: | Mega, T.; Lupia, M.; Amodio, N.; Horton, S. J.; Mesuraca, M.; Pelaggi, D.; Agosti, V.; Grieco, M.; Chiarella, E.; Spina, R.; Moore, M. A. S.; Schuringa, J. J.; Bond, H. M.; Morrone, G. |
| Article 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 N-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 carboxylterminal 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. © 2011 Landes Bioscience. |
| Keywords: | controlled study; unclassified drug; human cell; promoter region; dna-binding proteins; nonhuman; protein domain; protein function; protein motif; protein analysis; animal cell; mouse; animals; mice; cell compartmentalization; reverse transcription polymerase chain reaction; cell maturation; carboxy terminal sequence; protein protein interaction; protein targeting; rna, small interfering; rna interference; cell differentiation; in vitro study; hela cell; hela cells; mice, inbred c57bl; b lymphocyte; cell lineage; b-lymphocytes; gene expression regulation; amino terminal sequence; cell strain hek293; promoter regions, genetic; transactivation; transcription; hematopoietic stem cells; murinae; inhibition kinetics; trans-activators; hematopoietic stem cell; gene silencing; lymphopoiesis; zinc finger protein; histone deacetylases; binding competition; histone deacetylase; differentiation; lymphoid cell; zinc fingers; hek293 cells; ebf1; znf521; b lymphocyte differentiation factor; early b cell factor 1; zinc finger protein 521 |
| Journal Title: | Cell Cycle |
| Volume: | 10 |
| Issue: | 13 |
| ISSN: | 1538-4101 |
| Publisher: | Taylor & Francis Inc. |
| Date Published: | 2011-07-01 |
| Start Page: | 2129 |
| End Page: | 2139 |
| Language: | English |
| DOI: | 10.4161/cc.10.13.16045 |
| PROVIDER: | scopus |
| PUBMED: | 21593590 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 17 August 2011" - "Source: Scopus" |
