Zinc finger protein 521 antagonizes early B-cell factor 1 and modulates the B-lymphoid differentiation of primary hematopoietic progenitors
| Autor: | Malcolm A.S. Moore, Michele Grieco, Daniela Pelaggi, Tiziana Mega, Emanuela Chiarella, Nicola Amodio, Heather M. Bond, Giovanni Morrone, Michela Lupia, Maria Mesuraca, Raffaella Spina, Valter Agosti, Sarah J. Horton, Jan Jacob Schuringa |
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| Přispěvatelé: | Stem Cell Aging Leukemia and Lymphoma (SALL) |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Biology
Histone Deacetylases LINEAGE SPECIFICATION Mice Transactivation TRANSCRIPTION FACTOR EBF B-lymphocytes Animals Humans Gene silencing Cell Lineage Lymphopoiesis RNA Small Interfering Progenitor cell Promoter Regions Genetic Molecular Biology CEREBELLAR DEVELOPMENT GENE-EXPRESSION Zinc finger Regulation of gene expression EBF1 REPRESSION Zinc Fingers Cell Biology differentiation STEM Molecular biology Mi-2/NuRD complex Cell biology hematopoietic stem cells DNA-Binding Proteins Mice Inbred C57BL ZFP423 HEK293 Cells ZFP521 Gene Expression Regulation EVI3 Trans-Activators Histone deacetylase ZNF521 transcription LEUKEMIA HeLa Cells Developmental Biology |
| Zdroj: | Cell Cycle, 10(13), 2129-2139. Taylor & Francis Group |
| ISSN: | 1538-4101 |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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