Identification of Human GATA-2 Gene Distal IS Exon and Its Expression in Hematopoietic Stem Cell Fractions

Pan, Xiaoqing; Minegishi, Naoko; Harigae, Hideo; Yamagiwa, Hironori; Minegishi, Masayoshi; Akine, Yasuyuki; Yamamoto, Masayuki

doi:10.1093/oxfordjournals.jbchem.a022570

Cited by 59 publications

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“…CCAAT boxes in the IG promoter of the Gata2 gene 28 likely activate the transcription of the Gata2 gene as in the case with S-G 2 /M-specific genes, 56,57 while the IS promoter activates the transcription of the Gata2 gene in G 0 phase hematopoietic stem cells. [28][29][30] GATA2 and GATA1 compete for occupancy of the same GATA-binding motifs in the Gata2 gene, and GATA2 enhances, but GATA1 represses, its transcription. 46,58,59 We previously demonstrated stable GATA1 expression (half-life Ͼ 6 hours) in erythroid leukemia cells, 31 in contrast to the rapid degradation of GATA2.…”

Section: Discussionmentioning

confidence: 99%

“…on May 10, 2018. by guest www.bloodjournal.org From when expressed in hematopoietic progenitor cells derived from embryonic stem cells. 27 GATA2 is expressed both in quiescent and proliferating hematopoietic stem/progenitor cells [28][29][30] and is rapidly degraded through ubiquitination-proteasome-dependent systems. 31 We found marked variation in GATA2 staining among cultured cells, 31 suggesting cell-to-cell fluctuations in GATA2 expression.…”

Section: Introductionmentioning

confidence: 99%

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Cell-cycle–dependent oscillation of GATA2 expression in hematopoietic cells

Koga

Yamada

Abe

et al. 2007

Blood

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In vitro manipulation of hematopoietic stem cells (HSCs) is a key issue in both transplantation therapy and regenerative medicine, and thus new methods are required to achieve HSC expansion with self-renewal. GATA2 is a transcription factor controlling pool size of HSCs. Of interest, continuous overexpression of GATA2 does not induce HSC proliferation. In this report, we demonstrate that GATA2 expression, in leukemic and normal hematopoietic cells, oscillates during the cell cycle, such that expression is high in S phase but low in G 1 /S and M phase.GATA2 binding to target Bcl-X gene also oscillates in accordance with GATA2 expression. Using a green fluorescent protein (GFP)-GATA2 fusion protein, we demonstrate cell-cycle-specific activity of proteasome-dependent degradation of GATA2. Immunoprecipitation/immunoblotting analysis demonstrated phosphorylation of GATA2 at cyclin-dependent kinase (Cdk)-consensus motifs, S/T 0 P ؉1 , and interaction of GATA2 with Cdk2/ cyclin A2-, Cdk2/cyclin A2-, and Cdk4/ cyclin D1-phosphorylated GATA2 in vitro. Mutants in phosphorylation motifs exhibited altered expression profiles of GFP-GATA2 domain fusion proteins. These results indicate that GATA2 phosphorylation by Cdk/cyclin systems is responsible for the cell-cycle-dependent regulation of GATA2 expression, and suggest the possibility that a cell-cycle-specific "onoff" response of GATA2 expression may control hematopoietic-cell proliferation and survival. IntroductionHematopoietic stem cells (HSCs) give rise to the immunohematopoietic system throughout the lifetime of host animals. 1 HSCs have distinctive systems regulating their proliferation and differentiation. These systems maintain steady-state hematopoiesis, and respond to stresses, including infection, hypoxia, and blood loss. 1,2 Two types of cell division occur in HSCs: one type produces differentiated daughter cells to supply mature blood cells, while the other type reproduces HSCs (self-renewal division) to maintain life-long hematopoiesis. 1,2 Of interest, in the bone marrow reservoir of HSCs, more than 70% of bone marrow HSCs are quiescent (G 0 phase), maintaining high proliferative capacity and pluripotency. 3 In contrast, their quiescent mature progeny generally lack the capacity for growth and division.Directing the expansion of HSCs in vitro is an urgent problem that must be solved to meet the needs of transplantation therapy and to fulfill the promise of regenerative medicine. 4 HSC self-renewal and maturation divisions appear to be controlled, at least in part, by transcription factors (MEL/ELF4, 5 Gfi1 6,7 ), and also by cellcycle regulatory factors (cyclin-dependent kinase (Cdk) inhibitor, p21 Cip1/Waf1 , 8 p18 INK4C 9 phosphatase and tensin homologue (PTEN), 10 c-Myc, 11 and Myc antagonist, Mad 1 12 ). Analysis of mice deficient in Gfi1, 6,7 p21 Cip1/Waf1 , 8 or PTEN 10 revealed increased marrow HSC cycling and subsequent exhaustion of HSCs, and suggest possible cooperation between transcription factors and cell-cycle regulators.GATA2 is a member of th...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cell-cycle–dependent oscillation of GATA2 expression in hematopoietic cells

Koga

Yamada

Abe

et al. 2007

Blood

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“…The GATA family gene organization is highly conserved (12,13). Murine GATA-1 (14), mouse and human GATA-2 (13,15), chicken GATA-5 (16,17), and GATA-6 (18) each contains two distinct promoters and alternate first exons that independently regulate gene expression in distinct tissues or cell lineages.…”

Section: In Naive Cd4mentioning

confidence: 99%

Cutting Edge: Identification of an Alternative GATA-3 Promoter Directing Tissue-Specific Gene Expression in Mouse and Human

Asnagli

Afkarian

Murphy

2002

The Journal of Immunology

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The GATA family of transcription factors regulates development of multiple tissues. Several GATA factors have two promoters directing distinct tissue-specific expression. Although GATA-3 acts in both neuronal and thymocyte development, no alternative promoter usage has been reported. We examined various cell types and tissues for potential alternative GATA-3 transcripts and identified an alternative transcript directed by a promoter located 10 kb upstream of the recognized promoter. Sequences within this promoter and alternative first exon are highly conserved between mouse and human genomes. This new promoter is expressed selectively in the brain but is essentially undetectable in the thymus. In contrast, the recognized promoter is selectively expressed in the thymus but not in the brain. We also observed a gradual increase in expression from this new promoter during Th2 development. These results indicate that similar to other GATA factors, the GATA-3 gene can be controlled by two promoters that may direct lineage- and tissue-specific expression.

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“…22 In order to confirm that hESC derived endothelial cells have a correct imprint of epigenetic status we compared methylation profiles of regulatory regions of GATA-2,-3, and eNOS genes in hESCs, hESCs-derived endothelial cells, and HUVEC. We investigated the methylation status of each CpG in the selective GATA-2 promoter region (43 bp up to -187 bp from the translation start site designated as +1) 24 by sodium bisulfite genomic sequencing. In undifferentiated hESCs this region was heavily methylated exhibiting almost 80% methylation (Fig.…”

Section: Resultsmentioning

confidence: 99%