Induction of Erythrocyte Protein 4.2 Gene Expression during Differentiation of Murine Erythroleukemia Cells

Karaçay, Bahri; Chang, Long-Sheng

doi:10.1006/geno.1999.5846

Cited by 10 publications

(10 citation statements)

References 78 publications

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“…Further, P4.2 expression closely overlaps that of Tal1 at sites of erythropoiesis in embryonic and adult mice (63). Finally, the region of the P4.2 promoter containing these E box GATA elements was shown to be important in activating transcription of the gene during MEL cell differentiation (25).…”

Section: Resultsmentioning

confidence: 99%

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Identification of a TAL1 Target Gene Reveals a Positive Role for the LIM Domain-Binding Protein Ldb1 in Erythroid Gene Expression and Differentiation

Xu¹,

Huang²,

Chang

et al. 2003

Molecular and Cellular Biology

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127

158

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The TAL1 (or SCL) gene, originally identified from its involvement by a recurrent chromosomal translocation, encodes a basic helix-loop-helix transcription factor essential for erythropoiesis. Although presumed to regulate transcription, its target genes are largely unknown. We show here that a nuclear complex containing TAL1, its DNA-binding partner E47, zinc finger transcription factor GATA-1, LIM domain protein LMO2, and LIM domain-binding protein Ldb1 transactivates the protein 4.2 (P4.2) gene through two E box GATA elements in its proximal promoter. Binding of this complex to DNA was dependent on the integrity of both E box and GATA sites and was demonstrated to occur on the P4.2 promoter in cells. Maximal transcription in transiently transfected cells required both E box GATA elements and expression of all five components of the complex. This complex was shown, in addition, to be capable of linking in solution double-stranded oligonucleotides corresponding to the two P4.2 E box GATA elements. This DNA-linking activity required Ldb1 and increased with dimethyl sulfoxide-induced differentiation of murine erythroleukemia (MEL) cells. In contrast, enforced expression in MEL cells of dimerization-defective mutant Ldb1, as well as wild-type Ldb1, significantly decreased E box GATA DNA-binding activities, P4.2 promoter activity, and accumulation of P4.2 and ␤-globin mRNAs. These studies define a physiologic target for a TAL1-and GATA-1-containing ternary complex and reveal a positive role for Ldb1 in erythroid gene expression and differentiation.Red blood cell production is controlled by the concerted actions of signal transducers and nuclear regulators. Genetargeting studies have demonstrated a requirement for several nuclear proteins in erythropoiesis, including the TAL1 (or SCL) and GATA-1 transcription factors and the LIM domain protein LMO2. These proteins, singly and in combination, bind to specific promoter and enhancer elements to regulate the expression of genes that execute the differentiation program.

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Section: Resultsmentioning

confidence: 99%

“…The pGL2-P4.2p1700-Luc reporter plasmid was described previously (25). Plasmids pEFIRES-P and pEFIRES-N were provided by Stephen Hobbs (Institute of Cancer Research, London, United Kingdom), pCMV-E47 was provided by Gregory Kato (Johns Hopkins University, Baltimore, Md.…”

Section: Methodsmentioning

confidence: 99%

Identification of a TAL1 Target Gene Reveals a Positive Role for the LIM Domain-Binding Protein Ldb1 in Erythroid Gene Expression and Differentiation

Xu¹,

Huang²,

Chang

et al. 2003

Molecular and Cellular Biology

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127

158

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“…[22][23][24][25][26][27] It has been reported that cis-regulatory loci in membrane protein genes are cooccupied by GATA1 and FOG1 in erythroid cells. 28 Because membrane proteins progressively accumulate during erythroid differentiation, 29 we hypothesized that accumulation of such proteins might be modified by an imbalance of erythroid differentiation status and/or ineffective erythropoiesis.…”

Section: Interaction Of Gata1 and Fog1 Is Crucial For Membrane Proteimentioning

confidence: 99%

Mature erythrocyte membrane homeostasis is compromised by loss of the GATA1-FOG1 interaction

Hasegawa¹,

Shimizu

Mohandas

et al. 2012

Blood

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GATA1 plays essential roles in erythroid gene expression. The N-terminal finger of GATA1 (GATA1-Nf) is important for association with FOG1. Substitution mutations in GATA1-Nf, such as GATA1 V205M that diminish the GATA1-FOG1 association, have been identified in human thrombocytopenia and anemia cases. A mouse model of human thrombocytopenia has been established using a transgenic complementation rescue approach; GATA1-deficient mice were successfully rescued from embryonic lethality by excess expression of GATA1 V205G , but rescued adult mice suffered from severe thrombocytopenia. In this study, we examined GATA1-deficient mice rescued with GATA1 V205G at a comparable level to endogenous GATA1. Mice rescued with this level of GATA1 V205G rarely survive to adulthood. Rescued newborns suffered from severe anemia and jaundice accompanied with anisocytosis and spherocytosis. Expression of Slc4a1, Spna1, and Aqp1 genes (encoding the membrane proteins band-3, ␣-spectrin, and aquaporin-1, respectively) were strikingly diminished, whereas expression of other canonical GATA1-target genes, such as Alas2, were little affected. Lack of these membrane proteins provoked perturbation of membrane skeleton. Importantly, the red cells exhibited increased reactive oxygen species accumulation. These results thus demonstrate that the loss of the GATA1-FOG1 interaction causes a unique combination of membrane protein deficiency and disturbs the function of GATA1 in maintaining erythroid homeostasis. IntroductionGATA1 is a founding member of the GATA family of transcription factors. Because GATA1, GATA2, and GATA3 are highly expressed in hematopoietic lineages, these factors are collectively referred to as hematopoietic GATA factors. 1 The expression of hematopoietic GATA factor genes are strictly regulated through distinct molecular mechanisms, consequently each GATA molecule shows specificity in its expression profile. 1 In particular, GATA1 is expressed in lineage-committed cells, such as erythroid, megakaryocytic, eosinophilic, mast, and dendritic cells. 2,3 GATA1 plays key roles in regulating the differentiation and survival of these hematopoietic lineage cells. Targeted knockout of the Gata1 gene leads to in utero lethality of the mutant embryos because of defects in primitive and definitive hematopoiesis. 4,5 Conditional Gata1 gene knockout gives rise to red cell aplasia and severe thrombocytopenia. 6 In addition, GATA1 dysfunction is predictive of specific leukemias in mice and humans. 2 GATA1 contains 3 functional domains, that is an N-terminal transactivation (NT) domain, an N-terminal zinc finger (Nf) domain, and a C-terminal zinc finger (cf) domain. 7 These 3 domains have been shown to be important for GATA1 function. 7 In transgenic complementation rescue analyses, GATA1 lacking either the Nf or cf domain poorly rescues GATA1-deficient mice from embryonic lethality, which indicates the importance of both Nf and cf domains in GATA1 function in vivo. 7 The Nf domain interacts with FOG1 (friend of GATA1), and also stabilizes...

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“…P4.2 is an important component of the red cell membrane skeleton 57 and its expression is tightly regulated during erythroid differentiation. 58 Humans with inherited mutations in this gene and mice homozygous for a targeted mutation of the locus exhibit defective erythrocyte ion transport and spherocytic anemia. [59][60][61] the Dna-binding activity of the LDB-Gata complex and resultant P4.2 gene expression increase with erythroid differentiation 44 and are very sensitive to the levels of ssDP2.…”

confidence: 99%

Modularity of CHIP/LDB transcription complexes regulates cell differentiation

Bronstein

Segal

2011

Fly

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Induction of Erythrocyte Protein 4.2 Gene Expression during Differentiation of Murine Erythroleukemia Cells

Cited by 10 publications

References 78 publications

Identification of a TAL1 Target Gene Reveals a Positive Role for the LIM Domain-Binding Protein Ldb1 in Erythroid Gene Expression and Differentiation

Identification of a TAL1 Target Gene Reveals a Positive Role for the LIM Domain-Binding Protein Ldb1 in Erythroid Gene Expression and Differentiation

Mature erythrocyte membrane homeostasis is compromised by loss of the GATA1-FOG1 interaction

Modularity of CHIP/LDB transcription complexes regulates cell differentiation

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