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1 Citations
Facts about Erythroid transcription factor.
Activates the transcription of genes involved in erythroid differentiation of K562 erythroleukemia cells, such as HBB, HBG1/2, ALAS2 and HMBS (PubMed:24245781). .
Human | |
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Gene Name: | GATA1 |
Uniprot: | P15976 |
Entrez: | 2623 |
Belongs to: |
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No superfamily |
Eryf1; ERYF1GATA-binding protein 1 (globin transcription factor 1); GATA binding protein 1 (globin transcription factor 1); GATA1; GATA-1; GATA-1erythroid transcription factor; GATA-binding factor 1; GF-1; GF1globin transcription factor 1; NF-E1 DNA-binding protein; NFE1erythroid transcription factor 1; transcription factor GATA1; XLTT
Mass (kDA):
42.751 kDA
Human | |
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Location: | Xp11.23 |
Sequence: | X; NC_000023.11 (48786540..48794311) |
Erythrocytes.
Nucleus.
GATA1 is a sensitive lineage marker for erythroid and megakaryocytic precursor cells. This makes it especially useful in the characterization of acute and pure erythroid leukemias. Learn more about GATA1 and its various uses in this article. Also, learn about its role in erythroid differentiation. This article will review some of the best uses for GATA1.
A novel gene GATA1 binds to the DNA of erythroid and megakaryocytic-derived cells. Mutations in GATA1 impair the maturation of megakaryocyte-erythroid progenitors. These findings identify a novel role for GATA1 in hematopoiesis, and shed light on human GATA1 mutations, which promote megakaryocytic leukemia, a type of acute megakaryoblastic leukemia.
The gene is widely expressed and is a sensitive lineage marker for hematopoietic precursors. In mice, GATA1 is produced as two isoforms by alternative translation of one mRNA. This allows individual regulation of GATA1 levels, and isoform usage in certain haematopoietic lineages and stages. The present study investigated three fundamental questions about the GATA1 isoforms:
Mutations in GATA1 impair the interaction of the gene with FOG-1, a sensitive marker of megakaryocytic differentiation. Mutations in GATA1 impair FOG-1 binding in patients with X-linked thrombocytopenia and variable anemia. Although GATA1 is a sensitive lineage marker, its sensitivity to GATA1 expression is a concern.
While erythroid and megakaryocyte precursors share similar genetic profiles, these cells differ in their expression of transcription factors. In contrast, megakaryocytes express unique transcription factors, so there is no single factor that determines lineage choice. However, the action of multiple nuclear proteins may determine the final lineage of MEPs.
Mutations in GATA1 also impair the differentiation of hematopoietic cells. Pure erythroleukemia and acute megakaryoblastic leukemia exhibit intense nuclear GATA1 positivity. The remaining categories of acute myeloid leukemia are negative. Mutations in GATA1 are absent in plasma cells and metastatic carcinomas.
Multiple lines of evidence support the notion that GATA1 is a sensitive lineage-specific gene, regulated at multiple levels. Extracellular signals activate intracellular signaling pathways that regulate gene expression, which regulates cell differentiation. Ets-binding proteins, such as GATA1, act as chromatin modifiers and TFs. They largely define the transcriptome at a given stage.
Flow-cytometry analysis has shown that erythroid and megakaryoblast markers do not co-express on the same cell, and that erythroid and megakaryocyte cells mature in separate cells. The GFP expression level is used as a surrogate for GATA-1 protein level. Typically, intermediate and higher levels of GATA-1 indicate optimal erythroid and megakaryocytic maturation.
The gene product GATA1 is encoded by a polypeptide that contains two functional finger domains and an N-terminal transactivation domain. The finger domain is required for DNA binding and interactions with co-factors. In mouse cells, GATA1 is able to bind to DNA by binding to CACCC sequences that flank the start of the gene. However, this transcription factor is inactive in NIH/3 T3 cells, which lack endogenous GATA-1.
In addition, GATA1 is a sensitive marker of erythrocytic and megakaryocytic precursor cells. This is especially useful in the characterization of acute megakaryoblastic leukemia and pure erythroleukemia. Although GATA1 is absent in neoplastic cells, it can be found in some tumors. There are several other uses for GATA1 in leukemia research.
GATA1 is a zinc finger transcription factor that regulates a series of genes related to the development of erythroid progenitor cells. Proper erythroid development requires a well-organized regulation of these genes. In mice with a deficient GATA1 gene, improper Gata1 gene expression disrupts the balance between erythroid progenitor cell proliferation, survival, and differentiation. In contrast, mice with a functional GATA1 gene expression are able to produce normal, functional erythropoiesis.
While GATA1 has been shown to promote the synthesis of erythroid cells, the gene also regulates autophagy and exosome genes. It may coordinate these processes with erythropoiesis by binding to the GATA1 hematopoietic regulatory domain. The GATA1 hematopoietic regulatory domain is found between 3.9 and 2.6 kb upstream of the IE exon.
A mutation in the GATA1 gene is thought to be a critical event in the development of AMKL and TMD. The mutation occurs in the GATA1 gene, which is involved in the maturation of megakaryocyte lines. Although mutations in GATA1 cannot distinguish between TMD and AMKL, they can help in determining the underlying cause of the disease. Both TMD and early and delayed AMKL can be caused by identical mutations in the GATA gene.
The function of GATA1 is unclear, but it is a key transcription factor in erythropoiesis. Moreover, there are several hypoxia-inducible factors (HIF) proteins that play a critical role in upregulating gata1 expression. For example, hif1a binds to the promoter region of gata1 (CpG-rich element). The loss of HIFI genes results in inadequate expression of GATA1 in erythropoiesis.
The GATA1 gene is required for eryroid and megakaryocellular differentiation, and its inactivation results in a disorder of adult stem cell homeostasis. GATA-1 is regulated by distinct regulatory mechanisms during definitive erythropoiesis. Loss of the IE exon results in variant transcript expression and the production of a GATA1 protein that lacks its N-terminal domain.
Several research groups have investigated GATA1 in relation to these processes. The two genes display partially overlapping expression patterns. The GATA1 promoter, like Pit1, is a conserved element of the GATA network. The gene also regulates transcription. In addition, GATA1 promoters regulate erythroid and megakaryocytic differentiation.
A transgenic mouse model with defective GATA1 shows inadequate repression during eryroid and megakaryocrytic differentiation. The GATA1 gene has been found to be required for both eryroid and megakaryocytic differentiation, despite the lack of any clear functional role for it in this process. Nonetheless, there are many unanswered questions about its function.
Recent studies have also demonstrated that GATA1 is essential for eryroid as well as megakaryocytic differentiation. These results suggest that inflammatory cytokaryocytic determinants might bias HSCs towards the megakaryocytic lineage. Therefore, further investigation is necessary to determine how these factors impact megakaryopoiesis.
While GATA1FL expression was largely constant throughout the differentiation process, GATA1s were significantly upregulated at day two. DNA ploidy and induction of megakaryocytic genes are indicators of successful differentiation. Further studies are needed to determine how GATA1s function during the differentiation process. These findings have important implications for research on the role of GATA1 in haematopoietic differentiation.
The CP2-binding motif on the GATA1 gene promoter regulates erythroid-specific gene expression. The CP2-binding motif is required for enhanced transcription of globin-specific genes in erythroid cells. The CP2-binding motif is also essential for the differentiation of megakaryocytic stem cells. Thus, both GATA1 and GATA2 play important roles during erythropoiesis.
The gene GATA1 encodes a protein essential for erythroid and megakaryocyte differentiation and lineage specification. This gene was evaluated in both acute leukemia and normal marrow samples to determine whether GATA1 serves as a specific marker for these lineages. GATA1 expression was evaluated in bone marrow biopsy specimens of patients with acute leukemia.
In patients with RA, anemia is almost universal and is associated with an ineffective reticulocyte response. In the absence of reticulocyte response, the mean corpuscular volume is normal or may be increased in macrocytic myelocytes. The ratio of hemoglobin to cell size is usually normal. Absolute neutropenia and a circulating immature neutrophil population can also be found. This condition is called promythenia, and it accounts for less than 20 percent of the leukocyte differential.
The study showed that patients with a somatic mutation of GATA1 are predisposed to a transient myeloproliferative disease, known as TMD. In approximately 30% of these cases, the disease evolves into acute pediatric megakaryoblastic leukemia. The mutations in GATA1 map to exon 2, introduce a STOP codon, and alter splicing. Nearly all patients with DS-TMD have loss of GATA1-FL.
The findings show that GATA1 is a gene that regulates the growth and differentiation of hematopoietic cells. In addition, it suppresses the transformation of hematopoid cells and lymphoid cells. It is important to note that GATA1 is only one of the genes involved in erythroid and megakaryocytic differentiation.
The gene has been associated with the PU.1 transcription factor. This protein regulates erythroid differentiation and ETS-domain-DNA interaction. However, it is not known whether GATA1 is responsible for the PU.1 gene-based transcription of c-fms. This finding has important implications for the study of acute leukemia.
The gene is expressed in erythroid and megakaryoblast cells of acute leukemia. Consequently, GATA1FL may play a role in terminal differentiation of megakaryocytic cells. However, GATA1FL expression is not exclusively restricted to megakaryocytic cells, and this lack of exclusive cellular distribution suggests that GATA1FL is not the primary marker for lineage specification.
PMID: 2104960 by Trainor C.D., et al. Structure and evolution of a human erythroid transcription factor.
PMID: 2300555 by Zon L.I., et al. The major human erythroid DNA-binding protein (GF-1): primary sequence and localization of the gene to the X chromosome.
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