The GATA site-dependent hemogen promoter is transcriptionally regulated by GATA1 in hematopoietic and leukemia cells

Yang, Li V.; Wan, Junmei; Fu, Zhiyao; Kim, Sang Yong; Fujiwara, Yuko; Taub, Jeffrey W.; Matherly, Larry H.; Eliason, Jonathan L.; Li, L

doi:10.1038/sj.leu.2404105

Cited by 27 publications

(29 citation statements)

References 26 publications

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“…Our data indicate that cHEMGN acts as a transcription factor in the preSertoli cells to induce directly or indirectly SOX9 expression after sex determination. In the 5′-flanking region of mouse and human Hemgn/EDAG, binding sites for GATA1 (GATA binding protein 1) and HOXB4 (homeobox B4) (only reported in Hemgn) are present, and Hemgn/EDAG has been shown to be a direct transcriptional target of these genes in hematopoetic cells (22)(23)(24)(25). Future studies should determine the presence of a gonad-specific enhancer and transcription factors that mediate the gonadal expression of cHEMGN, as well as identify direct targets of cHEMGN.…”

Section: Expression In Masculinized Zw Gonads By Aromatase Inhibitormentioning

confidence: 99%

Chicken hemogen homolog is involved in the chicken-specific sex-determining mechanism

Nakata

Ishiguro

Aduma

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Using a comprehensive transcriptome analysis, a Z chromosomelinked chicken homolog of hemogen (cHEMGN) was identified and shown to be specifically involved in testis differentiation in early chicken embryos. Hemogen [Hemgn in mice, EDAG (erythroid differentiation-associated gene protein) in humans] was recently characterized as a hematopoietic tissue-specific gene encoding a transcription factor that regulates the proliferation and differentiation of hematopoietic cells in mammals. In chicken, cHEMGN was expressed not only in hematopoietic tissues but also in the early embryonic gonad of male chickens. The male-specific expression was identified in the nucleus of (pre)Sertoli cells after the sex determination period and before the expression of SOX9 (SRY-box 9). The expression of cHEMGN was induced in ZW embryonic gonads that were masculinized by aromatase inhibitor treatment. ZW embryos overexpressing cHEMGN, generated by infection with retrovirus carrying cHEMGN, showed masculinized gonads. These findings suggest that cHEMGN is a transcription factor specifically involved in chicken sex determination.bird | gonadal differentiation

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Section: Expression In Masculinized Zw Gonads By Aromatase Inhibitormentioning

confidence: 99%

Chicken hemogen homolog is involved in the chicken-specific sex-determining mechanism

Nakata

Ishiguro

Aduma

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…37 We, therefore, investigated whether other genes that demonstrated a correlation between monosomy 7 IKZF1 deletions in pediatric AML haematologica | 2015; 100 (9) 1155 Figure 2. Array comparative genomic hybridization analysis of monosomy 7 and focal IKZF1 deletions.…”

Section: © F E R R a T A S T O R T I F O U N D A T I O Nmentioning

confidence: 99%

Recurrent deletions of IKZF1 in pediatric acute myeloid leukemia

et al. 2015

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© F e r r a t a S t o r t i F o u n d a t i o nby controlling transcriptional regulators, such as GATA1 and RUNX1. 18,20 Although IKZF1 is not required for the initial differentiation towards granulocytes and monocytes, IKZF1 represses differentiation of the basophilic granulocyte lineage and promotes early maturation and survival of the neutrophil granulocyte lineage. 17,21,22 In pediatric AML, monosomy 7 is found in only 4%-5% of patients. The 5-year OS and EFS of pediatric AML patients with monosomy 7 with or without additional cytogenetic or chromosomal aberrations are poor. 23 In adult AML, monosomy 7 is the most frequent single monosomy and has a similar poor 4-year OS as compared to other single autosomal monosomies. 24 Deletions of the short arm of chromosome 7, 7p (del7p) were recurrently found in adult de novo AML and secondary AML developed from myelodysplastic syndrome (MDS) or myeloproliferative neoplasms (MPN). [25][26][27] Furthermore, 7p deletions were mapped to the IKZF1 locus and it was shown that loss of IKZF1 is acquired during the progression of MPN to secondairy AML, indicating that loss of IKZF1 contributes to the transformation from MPN to AML. 25 Together, these studies demonstrate that IKZF1 may play a role in myeloid differentiation and that loss of IKZF1 may contribute to myeloid oncogenesis. We, therefore, hypothesized that, in pediatric AML patients with monosomy 7, IKZF1 may be an important player. In this study, we analyzed the frequency of IKZF1 deletions in a pediatric AML cohort, and studied the difference in gene expression of cases with focal IKZF1 deletions, and cases with monosomy 7. Methods Patients' samplesSamples were provided by the Dutch Childhood Oncology Group (DCOG, the Netherlands), the AML-Berliner-FrankfurtMünster Study Group (Germany and Czech Republic), the SaintLouis Hospital (France), and the Royal Hospital for Sick Children (UK). Isolation of genomic DNA and total cellular RNA was performed using Trizol reagent. Each study group provided morphological and cytogenetic classification and clinical data. Institutional review board approval for these studies had been obtained in the participating centers. Detection of deletions and mutations of IKZF1Multiplex ligation-dependent probe amplification (MLPA) was performed using the p335-B1;ALL-IKZF1 kit (MRC Holland, Amsterdam, the Netherlands; data available at http: //www.mlpa.com). The data were analyzed with GeneMarker v. 1.85 (SoftGenetics, State College, Pennsylvania, USA). Data were normalized to reference probes and control samples. A deletion was defined as a peak ratio below 0.75; an amplification was defined as a peak ratio above 1.25.Array comparative genomic hybridization (Array-CGH) was performed using the human genome CGH Microarray 105K (Agilent Technologies, Santa Clara, California, USA) according to the manufacturer's protocol; data were analyzed with Genomic Workbench v. 5.0.14 (Agilent Technologies, Santa Clara, California, USA).Direct sequencing was used to analyze mutations or frameshif...

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“…1 Study of the regulation mechanism of its expression suggests that hemgn is a direct target of transcription factor GATA-1. 3 Moreover, hemgn is also expressed in testis in a variant splice form using an alternative promoter, suggesting a complex regulation mechanism of its expression. 4 Just like hemgn, EDAG is primarily expressed in immature precursors, such as CD34 þ progenitor cells, and is downregulated during maturation of blood cells.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of a hematopoietic transcriptional regulator EDAG induces myelopoiesis and suppresses lymphopoiesis in transgenic mice

et al. 2007

Leukemia

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Erythroid differentiation-associated gene (EDAG) is a hematopoietic tissue-specific gene that is highly expressed in the earliest CD34 þ lin À bone marrow (BM) cells and involved in the proliferation and differentiation of hematopoietic cells. To investigate the role of EDAG in hematopoiesis, we established an EDAG transgenic mouse model driven by human CD11a promoter. The transgenic mice showed increased mortality with severe organ infiltration by neutrophils, and the homeostasis of hematopoiesis was broken. The myelopoiesis was enhanced with expansion of myeloid cells in BM, increased peripheral granulocytes and extramedullary myelopoiesis in spleen. In contrast to myeloid cells, the lymphoid commitment was severely impaired with the B lymphopoiesis blocked at the transition from pro/pre-B I to pre-B II stage in BM and T thymocytes development blocked at the most immature stage (DN I). Moreover, we showed that EDAG was a transcriptional regulator which had transactivation activity and regulated the expression of several key transcription factors such as PU.1 and Pax5 in transgenic hematopoietic stem cells. These data suggested that EDAG was a key transcriptional regulator in maintaining the homeostasis of hematopoietic lineage commitment.

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The GATA site-dependent hemogen promoter is transcriptionally regulated by GATA1 in hematopoietic and leukemia cells

Cited by 27 publications

References 26 publications

Chicken hemogen homolog is involved in the chicken-specific sex-determining mechanism

Chicken hemogen homolog is involved in the chicken-specific sex-determining mechanism

Recurrent deletions of IKZF1 in pediatric acute myeloid leukemia

Overexpression of a hematopoietic transcriptional regulator EDAG induces myelopoiesis and suppresses lymphopoiesis in transgenic mice

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