• The GATA1 protein is involved in the specialization (differentiation) of immature blood cells. (medlineplus.gov)
  • Through its activity as a transcription factor and its interactions with other proteins, the GATA1 protein regulates the growth and division (proliferation) of immature red blood cells and platelet-precursor cells (megakaryocytes) and helps with their differentiation. (medlineplus.gov)
  • Divergent functions of hematopoietic transcription factors in lineage priming and differentiation during erythro-megakaryopoiesis. (uthsc.edu)
  • 9 ) The gene, located on chromosome X ( Xp11.23 ), encodes a key haematopoietic transcription factor involved in erythroid and megakaryocyte differentiation. (smj.org.sg)
  • Although studies have identified several miRNAs that regulate erythroid commitment and differentiation, we do not understand the mechanism by which the crucial erythroid transcription factors, GATA-1and NF-E2 directly regulate and control differentiation via miRNA pathways. (molcells.org)
  • Taken together, our results establish a functional link among the erythroid transcription factors GATA-1/NF-E2, miR-199b-5p and c-Kit, and provide new insights into the coupling of transcription and post-transcription regulation in erythroid differentiation. (molcells.org)
  • The up-regulation of miR-199b-5p during erythroid differentiation was dependent on the binding of GATA-1 and NF-E2 to its gene locus, which activated its transcription and maintained its high expression level in mature erythroid cells. (molcells.org)
  • In development, lineage-restricted transcription factors simultaneously promote differentiation while repressing alternative fates. (prolekarniky.cz)
  • Here, we have analyzed cis element regulation of the critical hematopoietic factor Gata2 , which is expressed in early precursors and repressed as GATA-1 levels rise during terminal differentiation. (prolekarniky.cz)
  • Although Gata2 is normally repressed in late-stage erythroblasts, the −1.8 kb mutation unexpectedly resulted in reactivated Gata2 transcription, blocked differentiation, and an aberrant lineage-specific gene expression pattern. (prolekarniky.cz)
  • Of the 29 patients who underwent GATA1 analysis, GATA1 mutations were observed in 15 (51.7%) patients, including 6 (75.0%) out of 8 patients with TAM, and 9 (42.9%) of 21 patients with ML-DS. (smj.org.sg)
  • In 4 AMKL patients multiple independent GATA1 mutations were observed. (ox.ac.uk)
  • Cells of the myeloid lineage, which include granulocytes, megakaryocytes, monocytes and macrophages, are derived from common myeloid progenitors, and are involved in such diverse roles as innate immunity and blood clotting. (wikipedia.org)
  • Inducible Gata1 suppression expands megakaryocyte-erythroid progenitors from embryonic stem cells. (uthsc.edu)
  • In addition to trisomy 21, fetal haemopoietic progenitors acquire N-terminal truncating mutations in the key megakaryocyte-erythroid transcription factor GATA1. (ox.ac.uk)
  • We here use conditional removal of the GATA-1 and FOG-1 transcription factors to identify FOG-1 as required for the formation of all committed Mk- and E-lineage progenitors, whereas GATA-1 was observed to be specifically required for E-lineage commitment. (ox.ac.uk)
  • We also observed differential effects of the four mutants on progenitors, myeloid cells and megakaryocytes. (biomedcentral.com)
  • GATA binding protein 1 (GATA1) is a transcription factor essential for effective erythropoiesis and megakaryopoiesis. (ox.ac.uk)
  • Coinciding with critical illness, we also identified an expansion of interferon-activated circulating megakaryocytes and increased erythropoiesis with features of hypoxic signaling. (embl.de)
  • An abnormal GATA1 protein causes immature red blood cells to undergo a form of programmed cell death called apoptosis. (medlineplus.gov)
  • This paved the way for the idea that given the right factors, our own differentiated cells can have their internal clocks turned back, to turn them back into a stem cell just like the one that makes all of those trillion cells that make us who we are, and one day we might be able to use them to grow tissues for transplant. (nhsbt.nhs.uk)
  • 2008). Historically, this concept is highlighted by the experi- factors are key intrinsic regulators of these fate decisions and mental phenomenon of lineage reprogramming, for example, that fate choice involves modulating networks of transcription by the conversion of fibroblasts to muscles cells following trans- factors. (lu.se)
  • In reality, gene somatic cells to a pluripotent cell state by a handful of transcrip- expression is graded, making the potential gene expression tion factors (Takahashi and Yamanaka, 2006). (lu.se)
  • Following lineage commitment, hematopoietic progenitor and precursor cells come increasingly under the regulatory influence of growth factors and hormones. (mhmedical.com)
  • The transcription factors that control lineage specification of haematopoietic stem cells (HSCs) have been well described for the myeloid and lymphoid lineages, whereas transcriptional control of erythroid (E) and megakaryocytic (Mk) fate is less understood. (ox.ac.uk)
  • CRISPR/Cas9-mediated TPM1 knockout in human induced pluripotent stem cells (iPSCs) enhanced hematopoietic progenitor development, increasing total megakaryocyte and erythroid cell yields. (biomedcentral.com)
  • To overcome this issue, we established immortalized megakaryocyte cell lines (imMKCLs) by introducing three transgenes, c-MYC, BMI1, and BCL-XL, sequentially into hematopoietic and megakaryocytic progenitor stage cells derived from iPSCs. (biomedcentral.com)
  • Platelets are released from megakaryocytes (MKs) in the bone marrow and circulate as anucleate blood cells with a diameter of about 2-4 μm. (biomedcentral.com)
  • Recent work using primary human foetal liver and bone marrow cells, human embryonic stem cells and iPS cells shows that prior to acquisition of GATA1 mutations, trisomy 21 itself alters human foetal haematopoietic stem cell and progenitor cell biology causing multiple abnormalities in myelopoiesis and B-lymphopoiesis. (ox.ac.uk)
  • Both GATA-1 and NF-E2 bound upstream of the miR-199b gene locus and activated its transcription. (molcells.org)
  • In the present study, we identified miR-199b-5p as a positive erythroid regulator, that was regulated by the key erythroid transcription factors GATA-1 and NF-E2. (molcells.org)
  • GATA factor cross-regulation represents an instructive model system for investigating the contribution of individual cis elements to the initiation and maintenance of transcriptional repression. (prolekarniky.cz)
  • The GATA family of transcription factors plays diverse roles in multiple developmental contexts [5] . (prolekarniky.cz)
  • GATA factors are often expressed in an overlapping but reciprocal pattern, such that expression of one GATA factor increases as expression of another decreases. (prolekarniky.cz)
  • For example, GATA-1 directly represses Gata2 transcription via displacing GATA-2 from chromatin sites at its own locus, a process termed a "GATA Switch" [6] , [7] . (prolekarniky.cz)
  • GATA factor function has been extensively studied in the context of hematopoiesis, where GATA-1, GATA-2, and GATA-3 are key regulators. (prolekarniky.cz)
  • The Friend of GATA (FOG) family of proteins are a highly-conserved family of large multitype zinc finger cofactors that bind to the amino zinc finger of GATA transcription factors, modulating their activity. (reactome.org)
  • Familial dyserythropoietic anaemia and thrombocytopenia due to an inherited mutation in GATA1. (uthsc.edu)
  • [ 6 ] an additional 10%-15% of newborns with DS have clinically silent disease with a low number of circulating blasts that have acquired a GATA1 mutation(s). (medscape.com)
  • While transcription factors bind and recruit chromatin-modifying and remodeling proteins, the relative contribution of individual cis elements residing within clusters of cis elements to the transcriptional control of endogenous loci is incompletely understood. (prolekarniky.cz)
  • These mutations, involving exons 2 or 3 of the GATA1 gene, result in synthesis of an aberrant truncated isoform (termed short GATA1 or GATA1s ) that is putatively oncogenic. (smj.org.sg)
  • Acquired mutations in megakaryocyte transcription factor GATA1 have recently been reported in Down syndrome (DS), transient myeloproliferative disorder (TMD), and acute megakaryoblastic leukemia (AMKL). (ox.ac.uk)
  • Cases of acute megakaryoblastic leukemia (AML, FAB M7) may show increased clusters of dysplastic megakaryocytes and micromegakaryocytes, and an increased number of megakaryoblasts, as shown in the following image. (medscape.com)
  • The fibrotic progression of both PV and ET was associated with a significant reduction in GATA1, particularly affecting the GATA1 full length isoform. (ox.ac.uk)
  • Increased expression of inflammatory cytokines, lysyl oxidase, transforming growth factor-β, impaired megakaryocyte function, and aberrant JAK-STAT signaling have all been implicated in the pathogenesis of bone marrow fibrosis. (haematologica.org)
  • Interestingly, three soluble factors released from imMKCLs in the turbulent flow condition, macrophage migration inhibitory factor (MIF), insulin growth factor binding protein 2 (IGFBP2), and nardilysin (NRDC), enhanced platelet production. (biomedcentral.com)
  • We herein report, to our knowledge, the first observation on the frequency and nature of GATA1 gene mutations in a cohort of Malaysian children with DS-associated TAM (n = 9) and ML-DS (n = 24) encountered successively over a period of five years at a national referral centre. (smj.org.sg)
  • The low frequency of GATA1 mutations in ML-DS patients is unusual and potentially indicates distinctive genomic events in our patient cohort. (smj.org.sg)
  • To assess whether an immunohistologic approach can be of help in separating different MPN, we have performed a comprehensive immunohistochemical evaluation of GATA1 expression in megakaryocytes within a cohort of BCR-ABL1 negative MPN. (ox.ac.uk)
  • N-terminal truncating mutations in the key haematopoietic transcription factor GATA1 are acquired during foetal life in virtually every case. (ox.ac.uk)
  • The GATA1 gene provides instructions for making a protein that attaches (binds) to specific regions of DNA and helps control the activity of many other genes. (medlineplus.gov)
  • On the basis of this action, the GATA1 protein is known as a transcription factor. (medlineplus.gov)
  • The fibrotic progression of pre-PMF to PMF was associated with a significant reduction of the overall GATA1 protein and a trend in reduction of GATA1s. (ox.ac.uk)
  • These studies reveal how an individual cis element establishes a normal developmental program via regulating specific steps in the mechanism by which a critical transcription factor is repressed. (prolekarniky.cz)
  • Reduced megakaryocytic expression of GATA1 has been linked to impaired hematopoiesis and bone marrow fibrosis in murine models and in vivo in patients affected by primary myelofibrosis (PMF). (ox.ac.uk)
  • These impairments in the GATA1 protein's normal function result in an increased proliferation of megakaryocytes and a decrease in mature platelets, leading to abnormal bleeding. (medlineplus.gov)
  • Results Our findings indicate that the platelets in HD are dysfunctional with respect to the release of angiogenic factors and functions including thrombosis, angiogenesis and vascular haemostasis. (bmj.com)
  • In vitro, MPL515/630 but not MPL515/625 or MPL515/625/630 retained the ability to induce TPO-independent proliferation and increase colony-forming unit megakaryocytes (CFU-Mk). (biomedcentral.com)
  • To provide novel insight into GATA1 mutations in DS, genomic DNA was assayed from 12 AMKL and 4 TMD cases (including neonatal, prediagnosis samples in 4 of 16), neonatal blood spots from 21 DS children without clinically evident TMD or AMKL, and 62 non-DS cord blood samples, using techniques not previously employed with such samples. (ox.ac.uk)
  • GATA1 mutations were present in all TMD and AMKL cases and at birth in 3 of 4 children without known clinical TMD, who later developed AMKL. (ox.ac.uk)
  • These data show GATA1 mutations occur in utero in most DS TMD and AMKL, that they may occur without clinical signs of disease, and that multiple separate GATA1 mutant clones can occur in an individual. (ox.ac.uk)
  • Chromosome 21 gene dosage effects and truncating mutations of the X-chromosomal transcription factor GATA1 synergize to trigger TMD and AMKL in most patients. (embl.de)
  • Natural history of GATA1 mutations in Down syndrome. (ox.ac.uk)
  • Description: The AFS98 monoclonal antibody reacts with the mouse CD115 molecule, a receptor for macrophage colony stimulating factor (M-CSF) or colony stimulating factor-1 (CSF-1). (thermofisher.com)
  • Transcription factors in these networks occupy specific cis elements at target gene loci where they modulate chromatin remodeling and modification, and thereby transcription. (prolekarniky.cz)
  • SATB1 Chromatin Loops Regulate Megakaryocyte/Erythroid Progenitor Expansion by Facilitating HSP70 and GATA1 Induction. (ucla.edu)
  • Molecular dissection of this process has been challenging as transcription factor loci are regulated by many trans -acting factors functioning through dispersed cis elements. (prolekarniky.cz)
  • Our findings support a role of GATA1 in the pathogenesis of BCR-ABL1 negative MPN, particularly in their fibrotic progression and suggest that the immunohistochemical evaluation of GATA1 may be of use in the differential diagnosis of these neoplasms. (ox.ac.uk)
  • 10 ) The mechanistic basis for somatic GATA1 mutations and the additional molecular events that determine progression from TAM to ML-DS are the focus of intense research. (smj.org.sg)
  • 8 ) An additional shared, critical pathogenetic event involves the acquisition of characteristic somatic mutations in the GATA1 gene. (smj.org.sg)
  • In vitro hematopoietic systems might be improved by identifying novel factors from human genetic studies. (biomedcentral.com)
  • In turn, this increased functional megakaryocyte (MK) yield. (biomedcentral.com)
  • The covalent modification of histones to yield specific histone marks promotes either the activation or repression of transcription [3] . (prolekarniky.cz)
  • However, data is limited regarding GATA1 expression in other myeloproliferative neoplasms (MPN) such as pre-fibrotic PMF (pre-PMF), polycythemia vera (PV) and essential thrombocythemia (ET) and in their respective fibrotic progression. (ox.ac.uk)
  • GATA1 gene mutations disrupt the protein's ability to bind with DNA or interact with other proteins. (medlineplus.gov)
  • Megakaryocyte- and erythroid-cell-derived co-expression modules were predictive of fatal disease outcome. (embl.de)
  • Our studies have revealed distinct features of tyrosine sites 625 and 630 in mediating MPL W515L-induced megakaryocyte hyperproliferation and MPNs. (biomedcentral.com)
  • Two isoforms of GATA1 exist, derived from alternative splicing. (ox.ac.uk)
  • This observational study attempts to characterise, for the first time, to our knowledge, the frequency and nature of somatic GATA1 mutations in DS children with TAM and ML-DS, encountered consecutively over a period of five years at a national paediatric oncology referral centre in Malaysia. (smj.org.sg)