GATA2 gene analysis in several forms of hematological malignancies including familial aggregations
Walid Sabri HamadouRahma ManiSawsen BesbesViolaine BourdonYosra Ben YoussefFrançois EisingerVéronique MariPaul GestaHélène DreyfusValérie BonadonaCatherine DugastHélène ZattaraLaurence FaivreT NoguchiAbderrahim KhélifHagay SobolZohra Soua
8
Citation
28
Reference
10
Related Paper
Citation Trend
Keywords:
GATA2
Genetic predisposition
Hematology
Animal model
Cite
Citations (1)
Long noncoding RNAs (lncRNA) are new, important players in gene regulation. We examined the role of lncRNA-GATA2: a novel, abundant, cytoplasmic, endothelial cell (EC)-enriched lncRNA divergently transcribed from the GATA2 transcription factor (TF). Interestingly, four of the six GATA TFs loci harbor a divergent lncRNA (GATA2, 3, 5 and 6).
We investigated whether lncRNA-GATA2 regulates EC phenotype and if this involves a relationship with GATA2. Loss-of-function studies demonstrated that lncRNA-GATA2 regulates 1374 EC genes. Several are EC-enriched, including ESM1, NOTCH4, vWF, and ANGPT2. lncRNA-GATA2 also controlled EC response to hypoxia through contrasting regulation of HIF1a and HIF2a. With respect to GATA2, lncRNA-GATA2 represses GATA2 protein. Importantly, we demonstrate lncRNA-GATA2 in GATA-family cross-talk and controlling the cell-specific GATA program, as lncRNA-GATA2 regulated the GATA TFs and associated lncRNAs. lncRNA-GATA2 regulates the EC phenotype in a context-dependent manner, through the regulation of enriched genes important for EC biology and the GATA family.%%%%M.Sc.
GATA2
GATA transcription factor
Cite
Citations (0)
Objective:To explore the possibility of secondary neoplasia following long term combined chemotherapy.Methods:Sister chromatid exchanges(SCE)were investigated in 44 patients with adult leukemia.Rusults:Frequencies of SCE in patients with de novo leukemia,relapsed leukemia and chronic myeloid leukemia(CML)were significant higher than health controls.The five patients(5/16)with complete remission showed higher SCE frequencies,those were mainly the patients received more than nine courses of combined chemotherapeutic regimens received more than nine courses of combined chemotherapeutic regimens.Conclusion:The patients with de novo leukemia,relapsed leukemia and CML have DNA damage in diagnosis,long term combined chemotherapy may cause the DNA instability in partial patients.
Sister chromatid exchange
Cite
Citations (0)
Transcription factor GATA 2 is highly expressed in hematopoietic stem cells and progenitors, whereas its expression declines after erythroid commitment of progenitors. In contrast, the start of GATA 1 expression coincides with the erythroid commitment and increases along with the erythroid differentiation. We refer this dynamic transition of GATA factor expression to as the ‘ GATA factor switching’. Here, we examined contribution of the GATA factor switching to the erythroid differentiation. In Gata1‐ knockdown embryos that concomitantly express Gata2 ‐ GFP reporter, high‐level expression of GFP reporter was detected in accumulated immature hematopoietic cells with impaired differentiation, demonstrating that GATA 1 represses Gata2 gene expression in hematopoietic progenitors in vivo . We have conducted chromatin immunoprecipitation (ChIP) on microarray analyses of GATA 2 and GATA 1, and results indicate that the GATA 1‐binding sites widely overlap with the sites pre‐occupied by GATA 2 before the GATA 1 expression. Importantly, erythroid genes harboring GATA boxes bound by both GATA 1 and GATA 2 tend to be expressed in immature erythroid cells, whereas those harboring GATA boxes to which GATA 1 binds highly but GATA 2 binds only weakly are important for the mature erythroid cell function. Our results thus support the contention that preceding binding of GATA 2 helps the following binding of GATA 1 and thereby secures smooth expression of the transient‐phase genes.
GATA2
GATA1
GATA transcription factor
Cite
Citations (70)
The generation of mouse hematopoietic stem cells from hemogenic endothelial cells (HECs) in the aorta/gonad/mesonephros region of developing embryos requires a zinc finger transcription factor Gata2. In the previous study, an enforced expression of Gata2 in vitro promoted the production of HECs from mesodermal cells differentiated from mouse embryonic stem cells (ESCs). Our research group has previously demonstrated that the enforced expression of Gata2 in ESC-derived HECs enhances erythroid and megakaryocyte differentiation and inhibits macrophage differentiation. However, the manner in which the multiple functions of Gata2 are regulated remains unclear. Mouse ESCs differentiate into various types of hematopoietic cells when cocultured with OP9 stromal cells (OP9 system). Using this system and the inducible gene cassette exchange system, which facilitates the establishment of ESCs carrying inducible transgenes under an identical gene expression regulatory unit, the domain-specific functions of Gata2 were systematically dissected in this study. We determined that the N-terminal (amino acid 1-110) region of Gata2 was an erythroid-inducing region, both the middle (amino acid 111-200) and C-terminal (amino acid 413-480) regions were megakaryocyte-inducing regions. Furthermore, the present data strongly suggest that intramolecular antagonistic interactions between each of these regions fine-tune the biological functions of Gata2.
GATA2
GATA transcription factor
GATA1
Cite
Citations (7)
GATA2
GATA1
GATA transcription factor
GATA4
Cite
Citations (1)
GATA2 is a transcription factor that is critical for the generation and survival of hematopoietic stem cells (HSCs). It also plays an important role in the regulation of myeloid differentiation. Accordingly, GATA2 expression is restricted to HSCs and hematopoietic progenitors as well as early erythroid cells and megakaryocytic cells. Here we identified aberrant GATA2 expression in B-cell acute lymphoblastic leukemia (B-ALL) by analyzing transcriptome sequencing data obtained from St. Jude Cloud. Differentially expressed genes upon GATA2 activation showed significantly myeloid-like transcription signature. Further analysis identified several tumor-associated genes as targets of GATA2 activation including BAG3 and EPOR. In addition, the correlation between KMT2A-USP2 fusion and GATA2 activation not only indicates a potential trans-activating mechanism of GATA2 but also suggests that GATA2 is a target of KMT2A-USP2. Furthermore, by integrating whole-genome and transcriptome sequencing data, we showed that GATA2 is also cis activated. A somatic focal deletion located in the GATA2 neighborhood that disrupts the boundaries of topologically associating domains was identified in one B-ALL patient with GATA2 activation. These evidences support the hypothesis that GATA2 could be involved in leukemogenesis of B-ALL and can be transcriptionally activated through multiple mechanisms. The findings of aberrant activation of GATA2 and its molecular function extend our understanding of transcriptional factor dysregulation in B-ALL.
GATA2
Cite
Citations (7)
GATA2
Cyclin A
GATA transcription factor
Cite
Citations (0)
Efforts have been made to understand how erythroid differentiation is regulated, and recent discoveries have clarified that lineage-specific transcription factor networks are essential for proper differentiation of erythroid cells. The transcription factors GATA1 and GATA2 are involved in such networks that regulate erythroid gene expression. Importantly, expression of Gata1 and Gata2 genes is also under the control of such regulatory networks. The present review is focused on the mechanism of Gata1 and Gata2 gene regulation during erythropoiesis and the physiological significance of their dynamic regulation.Gata1 and Gata2 genes are regulated by multiple transcription factors, including their own products GATA1 and GATA2. GATA1 and GATA2 recognize specific regulatory GATA motifs, and their expression levels change dynamically during erythroid differentiation, leading to diversified gene expression during erythropoiesis.Strict regulations of the Gata1 and Gata2 genes are critical for proper lineage commitment and development of erythroid cells. It has been shown in transgenic mouse analyses that cis-acting GATA binding motifs are critical for the expression of Gata1 and Gata2 genes. Furthermore, expression of Gata1 and Gata2 genes along with a set of erythroid genes appeared to be regulated by GATA factor switching.
GATA2
GATA1
GATA transcription factor
Cite
Citations (78)
Hematology
Hematology analyzer
Transfusion medicine
Cite
Citations (2)