GATA-related hematologic disorders

Shimizu, Ritsuko; Yamamoto, Masayuki

doi:10.1016/j.exphem.2016.05.010

Cited by 31 publications

(38 citation statements)

References 76 publications

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“…This may be also associated with the P. chabaudi-induced extramedullary hepatic erythropoiesis (Al-Quraishy et al 2016), since the enucleation of erythroblasts has been previously regarded as an asymmetric form of mitosis (Thompson et al 2010). Furthermore, hepatic erythropoiesis, in particular the differentiation to relatively mature erythroid progenitors (Shimizu and Yamamoto 2016), has been recently suggested to be critically controlled by the transcription factor GATA1 during the crisis phase of vaccination-protected mice (Al-Quraishy et al 2016). The onset of hepatic erythropoiesis is presumably at peak parasitemia (Krücken et al 2009;Al-Quraishy et al 2016), and this very early erythroid development is known to be controlled by GATA2, which even represses Gata1 (Suzuki et al 2011;Shimizu and Yamamoto 2016).…”

Section: Discussionmentioning

confidence: 97%

“…Furthermore, hepatic erythropoiesis, in particular the differentiation to relatively mature erythroid progenitors (Shimizu and Yamamoto 2016), has been recently suggested to be critically controlled by the transcription factor GATA1 during the crisis phase of vaccination-protected mice (Al-Quraishy et al 2016). The onset of hepatic erythropoiesis is presumably at peak parasitemia (Krücken et al 2009;Al-Quraishy et al 2016), and this very early erythroid development is known to be controlled by GATA2, which even represses Gata1 (Suzuki et al 2011;Shimizu and Yamamoto 2016). The switch from GATA2 to GATA1 has been suggested to be one of the key regulatory mechanisms underlying erythroid differentiation (Shimizu and Yamamoto 2016;Guo et al 2016).…”

Section: Discussionmentioning

confidence: 99%

“…The onset of hepatic erythropoiesis is presumably at peak parasitemia (Krücken et al 2009;Al-Quraishy et al 2016), and this very early erythroid development is known to be controlled by GATA2, which even represses Gata1 (Suzuki et al 2011;Shimizu and Yamamoto 2016). The switch from GATA2 to GATA1 has been suggested to be one of the key regulatory mechanisms underlying erythroid differentiation (Shimizu and Yamamoto 2016;Guo et al 2016). It is therefore not fortuitous that the promoter of Gata2 is found here to be down-methylated by both vaccination and P. chabaudi infections at peak parasitemia of vaccinated mice, which would allow a higher expression of Gata2 at the onset of hepatic erythropoiesis induced by P. chabaudi.…”

Section: Discussionmentioning

confidence: 99%

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Protective vaccination and blood-stage malaria modify DNA methylation of gene promoters in the liver of Balb/c mice

et al. 2017

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Epigenetic mechanisms such as DNA methylation are increasingly recognized to be critical for vaccination efficacy and outcome of different infectious diseases, but corresponding information is scarcely available for host defense against malaria. In the experimental blood-stage malaria Plasmodium chabaudi, we investigate the possible effects of a blood-stage vaccine on DNA methylation of gene promoters in the liver, known as effector against blood-stage malaria, using DNA methylation microarrays. Naturally susceptible Balb/c mice acquire, by protective vaccination, the potency to survive P. chabaudi malaria and, concomitantly, modifications of constitutive DNA methylation of promoters of numerous genes in the liver; specifically, promoters of 256 genes are hyper(=up)- and 345 genes are hypo(=down)-methylated (p < 0.05). Protective vaccination also leads to changes in promoter DNA methylation upon challenge with P. chabaudi at peak parasitemia on day 8 post infection (p.i.), when 571 and 1013 gene promoters are up- and down-methylated, respectively, in relation to constitutive DNA methylation (p < 0.05). Gene set enrichment analyses reveal that both vaccination and P. chabaudi infections mainly modify promoters of those genes which are most statistically enriched with functions relating to regulation of transcription. Genes with down-methylated promoters encompass those encoding CX3CL1, GP130, and GATA2, known to be involved in monocyte recruitment, IL-6 trans-signaling, and onset of erythropoiesis, respectively. Our data suggest that vaccination may epigenetically improve parts of several effector functions of the liver against blood-stage malaria, as, e.g., recruitment of monocyte/macrophage to the liver accelerated liver regeneration and extramedullary hepatic erythropoiesis, thus leading to self-healing of otherwise lethal P. chabaudi blood-stage malaria.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Protective vaccination and blood-stage malaria modify DNA methylation of gene promoters in the liver of Balb/c mice

et al. 2017

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“…Subsequent studies however have demonstrated that GATA1 exerts these functions in combinations with other proteins in complexes which may either promote or inhibit gene transcription depending on the context [26]. It has also been reported that the effects exerted by GATA1 on gene transcription depend on its concentration relative to another member of the GATA family, GATA2 [27]. For example, in the case of stem and progenitor cells, the level of GATA2 is far greater than that of GATA1, which tips the balance towards proliferation.…”

Section: Gata1 Regulates Transcription In Conjunction With Multiple Cmentioning

confidence: 99%

GATA1 insufficiencies in primary myelofibrosis and other hematopoietic disorders: consequences for therapy

Ling

Crispino

Zingariello

et al. 2018

Expert Review of Hematology

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Introduction: GATA1, the founding member of a family of transcription factors, plays important roles in the development of hematopoietic cells of several lineages. Although loss of GATA1 has been known to impair hematopoiesis in animal models for nearly 25 years, the link between GATA1 defects and human blood diseases has only recently been realized. Areas covered: Here the current understanding of the functions of GATA1 in normal hematopoiesis and how it is altered in disease is reviewed. GATA1 is indispensable mainly for erythroid and megakaryocyte differentiation. In erythroid cells, GATA1 regulates early stages of differentiation, and its deficiency results in apoptosis. In megakaryocytes, GATA1 controls terminal maturation and its deficiency induces proliferation. GATA1 alterations are often found in diseases involving these two lineages, such as congenital erythroid and/or megakaryocyte deficiencies, including Diamond Blackfan Anemia (DBA), and acquired neoplasms, such as acute megakaryocytic leukemia (AMKL) and the myeloproliferative neoplasms (MPNs). Expert Commentary: Since the first discovery of GATA1 mutations in AMKL, the number of diseases that are associated with impaired GATA1 function has increased to include DBA and MPNs. With respect to the latter, we are only just now appreciating the link between enhanced JAK/STAT signaling, GATA1 deficiency and disease pathogenesis.

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“…Cell-based complementation approaches have determined how the mutations alter the functions of GATA1 (25). Furthermore, genetically manipulated mouse models that phenocopy human diseases have been established and provide insight into the pathogenesis caused by GATA1 dysfunction (26–29). Furthermore, quantitative reduction of GATA1 has been described as causal in acute erythroblastic leukemia and myelofibrosis in mice (30–32).…”

Section: Introductionmentioning

confidence: 99%

GATA1 Activity Governed by Configurations of cis-Acting Elements

Hasegawa

Shimizu

2017

Front. Oncol.

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The transcription factor GATA1 regulates the expression of essential erythroid and megakaryocytic differentiation genes through binding to the DNA consensus sequence WGATAR. The GATA1 protein has four functional domains, including two centrally located zinc-finger domains and two transactivation domains at the N- and C-termini. These functional domains play characteristic roles in the elaborate regulation of diversified GATA1 target genes, each of which exhibits a unique expression profile. Three types of GATA1-related hematological malignancies have been reported. One is a structural mutation in the GATA1 gene, resulting in the production of a short form of GATA1 that lacks the N-terminal transactivation domain and is found in Down syndrome-related acute megakaryocytic leukemia. The other two are cis-acting regulatory mutations affecting expression of the Gata1 gene, which have been shown to cause acute erythroblastic leukemia and myelofibrosis in mice. Therefore, imbalanced gene regulation caused by qualitative and quantitative changes in GATA1 is thought to be involved in specific hematological disease pathogenesis. In the present review, we discuss recent advances in understanding the mechanisms of differential transcriptional regulation by GATA1 during erythroid differentiation, with special reference to the binding kinetics of GATA1 at conformation-specific binding sites.

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GATA-related hematologic disorders

Cited by 31 publications

References 76 publications

Protective vaccination and blood-stage malaria modify DNA methylation of gene promoters in the liver of Balb/c mice

Protective vaccination and blood-stage malaria modify DNA methylation of gene promoters in the liver of Balb/c mice

GATA1 insufficiencies in primary myelofibrosis and other hematopoietic disorders: consequences for therapy

GATA1 Activity Governed by Configurations of cis-Acting Elements

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