Number of the records: 1
EVI2B is a C/EBP alpha target gene required for granulocytic differentiation and functionality of hematopoietic progenitors
- 1.
SYSNO ASEP 0483248 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title EVI2B is a C/EBP alpha target gene required for granulocytic differentiation and functionality of hematopoietic progenitors Author(s) Zjablovskaja, Polina (UMG-J)
Kardošová, Miroslava (UMG-J)
Daněk, Petr (UMG-J)
Angelisová, Pavla (UMG-J) RID
Benoukraf, T. (SG)
Wurm, A.A. (DE)
Kalina, T. (CZ)
Sian, S. (SG)
Balaštík, Martin (FGU-C) RID, ORCID
Delwel, R. (NL)
Brdička, Tomáš (UMG-J) RID
Tenen, D.G. (US)
Malissen, B. (FR)
Behre, G. (DE)
Fiore, F. (FR)
Hořejší, Václav (UMG-J) RID
Alberich-Jorda, Meritxell (UMG-J) RIDNumber of authors 17 Source Title Cell Death and Differentiation. - : Springer - ISSN 1350-9047
Roč. 24, č. 4 (2017), s. 705-716Number of pages 12 s. Language eng - English Country GB - United Kingdom Keywords acute myeloid-leukemia ; binding protein-alpha ; cebpa mutations ; expression ; induction ; phosphorylation ; granulopoiesis ; cells ; block Subject RIV EB - Genetics ; Molecular Biology OECD category Cell biology Subject RIV - cooperation Institute of Physiology - Genetics ; Molecular Biology R&D Projects GAP303/12/0855 GA ČR - Czech Science Foundation (CSF) LM2015040 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) ED2.1.00/19.0395 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LQ1604 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support UMG-J - RVO:68378050 ; FGU-C - RVO:67985823 UT WOS 000397919400015 EID SCOPUS 85012120404 DOI 10.1038/cdd.2017.6 Annotation Development of hematopoietic populations through the process of differentiation is critical for proper hematopoiesis. The transcription factor CCAAT/enhancer binding protein alpha (C/EBP alpha) is a master regulator of myeloid differentiation, and the identification of C/EBPa target genes is key to understand this process. Here we identified the Ecotropic Viral Integration Site 2B (EVI2B) gene as a direct target of C/EBPa. We showed that the product of the gene, the transmembrane glycoprotein EVI2B (CD361), is abundantly expressed on the surface of primary hematopoietic cells, the highest levels of expression being reached in mature granulocytes. Using shRNA-mediated downregulation of EVI2B in human and murine cell lines and in primary hematopoietic stem and progenitor cells, we demonstrated impaired myeloid lineage development and altered progenitor functions in EVI2B-silenced cells. We showed that the compromised progenitor functionality in EvI2b-depleted cells can be in part explained by deregulation of cell proliferation and apoptosis. In addition, we generated an Evi2b knockout murine model and demonstrated altered properties of hematopoietic progenitors, as well as impaired G-CSF dependent myeloid colony formation in the knockout cells. Remarkably, we found that EVI2B is significantly downregulated in human acute myeloid leukemia samples characterized by defects in CEBPA. Altogether, our data demonstrate that EVI2B is a downstream target of C/EBPa, which regulates myeloid differentiation and functionality of hematopoietic progenitors. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2018
Number of the records: 1