The Pleiotropic Effects of GATA1 and KLF1 in Physiological Erythropoiesis and in Dyserythropoietic Disorders

Overview

Journal Front Physiol

Date 2019 Feb 28

PMID 30809156

Citations 12

Authors

Gloria Barbarani

Cristina Fugazza

John Strouboulis

Antonella E Ronchi

Affiliations

Soon will be listed here.

Abstract

In the last few years, the advent of new technological approaches has led to a better knowledge of the ontogeny of erythropoiesis during development and of the journey leading from hematopoietic stem cells (HSCs) to mature red blood cells (RBCs). Our view of a well-defined hierarchical model of hematopoiesis with a near-homogeneous HSC population residing at the apex has been progressively challenged in favor of a landscape where HSCs themselves are highly heterogeneous and lineages separate earlier than previously thought. The coordination of these events is orchestrated by transcription factors (TFs) that work in a combinatorial manner to activate and/or repress their target genes. The development of next generation sequencing (NGS) has facilitated the identification of pathological mutations involving TFs underlying hematological defects. The examples of GATA1 and KLF1 presented in this review suggest that in the next few years the number of TF mutations associated with dyserythropoietic disorders will further increase.

Citing Articles

Peak Scores Significantly Depend on the Relationships between Contextual Signals in ChIP-Seq Peaks.

Vishnevsky O, Bocharnikov A, Ignatieva E Int J Mol Sci. 2024; 25(2).

PMID: 38256085 PMC: 10816497. DOI: 10.3390/ijms25021011.

Myeloproliferative Neoplasms: Diseases Mediated by Chronic Activation of Signal Transducer and Activator of Transcription (STAT) Proteins.

Liongue C, Ward A Cancers (Basel). 2024; 16(2).

PMID: 38254802 PMC: 10813624. DOI: 10.3390/cancers16020313.

EHBP1L1, an apicobasal polarity regulator, is critical for nuclear polarization during enucleation of erythroblasts.

Wu J, Moriwaki K, Asuka T, Nakai R, Kanda S, Taniguchi M Blood Adv. 2023; 7(14):3382-3394.

PMID: 37042948 PMC: 10345855. DOI: 10.1182/bloodadvances.2022008930.

Genetic regulation of fetal hemoglobin across global populations.

Cato L, Li R, Lu H, Yu F, Wissman M, Mkumbe B medRxiv. 2023; .

PMID: 36993312 PMC: 10055601. DOI: 10.1101/2023.03.24.23287659.

Novel Variant Causing a Bleeding Phenotype Associated with Combined Platelet α-/δ-Storage Pool Deficiency and Mild Dyserythropoiesis Modified by a Variant.

Jurk K, Adenaeuer A, Sollfrank S, Gross K, Hauser F, Czwalinna A Cells. 2022; 11(19).

PMID: 36231035 PMC: 9564339. DOI: 10.3390/cells11193071.

References

Crispino J, Lodish M, Mackay J, Orkin S . Use of altered specificity mutants to probe a specific protein-protein interaction in differentiation: the GATA-1:FOG complex. Mol Cell. 1999; 3(2):219-28. DOI: 10.1016/s1097-2765(00)80312-3. View

Vyas P, Ault K, Jackson C, Orkin S, Shivdasani R . Consequences of GATA-1 deficiency in megakaryocytes and platelets. Blood. 1999; 93(9):2867-75. View

Perkins A, Peterson K, Stamatoyannopoulos G, Witkowska H, Orkin S . Fetal expression of a human Agamma globin transgene rescues globin chain imbalance but not hemolysis in EKLF null mouse embryos. Blood. 2000; 95(5):1827-33. View

Nichols K, Crispino J, Poncz M, White J, Orkin S, Maris J . Familial dyserythropoietic anaemia and thrombocytopenia due to an inherited mutation in GATA1. Nat Genet. 2000; 24(3):266-70. PMC: 10576470. DOI: 10.1038/73480. View

Manco L, Ribeiro M, Maximo V, Almeida H, Costa A, Freitas O . A new PKLR gene mutation in the R-type promoter region affects the gene transcription causing pyruvate kinase deficiency. Br J Haematol. 2000; 110(4):993-7. DOI: 10.1046/j.1365-2141.2000.02283.x. View

Solis C, Aizencang G, Astrin K, Bishop D, Desnick R . Uroporphyrinogen III synthase erythroid promoter mutations in adjacent GATA1 and CP2 elements cause congenital erythropoietic porphyria. J Clin Invest. 2001; 107(6):753-62. PMC: 208941. DOI: 10.1172/JCI10642. View

Freson K, Devriendt K, Matthijs G, Van Hoof A, De Vos R, Thys C . Platelet characteristics in patients with X-linked macrothrombocytopenia because of a novel GATA1 mutation. Blood. 2001; 98(1):85-92. DOI: 10.1182/blood.v98.1.85. View

Newton A, Mackay J, Crossley M . The N-terminal zinc finger of the erythroid transcription factor GATA-1 binds GATC motifs in DNA. J Biol Chem. 2001; 276(38):35794-801. DOI: 10.1074/jbc.M106256200. View

Mehaffey M, Newton A, Gandhi M, Crossley M, Drachman J . X-linked thrombocytopenia caused by a novel mutation of GATA-1. Blood. 2001; 98(9):2681-8. DOI: 10.1182/blood.v98.9.2681. View

10.

Freson K, Matthijs G, Thys C, Marien P, Hoylaerts M, Vermylen J . Different substitutions at residue D218 of the X-linked transcription factor GATA1 lead to altered clinical severity of macrothrombocytopenia and anemia and are associated with variable skewed X inactivation. Hum Mol Genet. 2002; 11(2):147-52. DOI: 10.1093/hmg/11.2.147. View

11.

Yu C, Cantor A, Yang H, Browne C, Wells R, Fujiwara Y . Targeted deletion of a high-affinity GATA-binding site in the GATA-1 promoter leads to selective loss of the eosinophil lineage in vivo. J Exp Med. 2002; 195(11):1387-95. PMC: 2193547. DOI: 10.1084/jem.20020656. View

12.

Chang A, Cantor A, Fujiwara Y, Lodish M, Droho S, Crispino J . GATA-factor dependence of the multitype zinc-finger protein FOG-1 for its essential role in megakaryopoiesis. Proc Natl Acad Sci U S A. 2002; 99(14):9237-42. PMC: 123124. DOI: 10.1073/pnas.142302099. View

13.

Vannucchi A, Bianchi L, Cellai C, Paoletti F, Rana R, Lorenzini R . Development of myelofibrosis in mice genetically impaired for GATA-1 expression (GATA-1(low) mice). Blood. 2002; 100(4):1123-32. DOI: 10.1182/blood-2002-06-1913. View

14.

Wechsler J, Greene M, McDevitt M, Anastasi J, Karp J, Le Beau M . Acquired mutations in GATA1 in the megakaryoblastic leukemia of Down syndrome. Nat Genet. 2002; 32(1):148-52. DOI: 10.1038/ng955. View

15.

Yu C, Niakan K, Matsushita M, Stamatoyannopoulos G, Orkin S, Raskind W . X-linked thrombocytopenia with thalassemia from a mutation in the amino finger of GATA-1 affecting DNA binding rather than FOG-1 interaction. Blood. 2002; 100(6):2040-5. PMC: 2808424. DOI: 10.1182/blood-2002-02-0387. View

16.

Mundschau G, Gurbuxani S, Gamis A, Greene M, Arceci R, Crispino J . Mutagenesis of GATA1 is an initiating event in Down syndrome leukemogenesis. Blood. 2003; 101(11):4298-300. DOI: 10.1182/blood-2002-12-3904. View

17.

Rainis L, Bercovich D, Strehl S, Teigler-Schlegel A, Stark B, Trka J . Mutations in exon 2 of GATA1 are early events in megakaryocytic malignancies associated with trisomy 21. Blood. 2003; 102(3):981-6. DOI: 10.1182/blood-2002-11-3599. View

18.

Xu G, Nagano M, Kanezaki R, Toki T, Hayashi Y, Taketani T . Frequent mutations in the GATA-1 gene in the transient myeloproliferative disorder of Down syndrome. Blood. 2003; 102(8):2960-8. DOI: 10.1182/blood-2003-02-0390. View

19.

Ahmed M, Sternberg A, Hall G, Thomas A, Smith O, OMarcaigh A . Natural history of GATA1 mutations in Down syndrome. Blood. 2003; 103(7):2480-9. DOI: 10.1182/blood-2003-10-3383. View

20.

Shimada A, Xu G, Toki T, Kimura H, Hayashi Y, Ito E . Fetal origin of the GATA1 mutation in identical twins with transient myeloproliferative disorder and acute megakaryoblastic leukemia accompanying Down syndrome. Blood. 2003; 103(1):366. DOI: 10.1182/blood-2003-09-3219. View