Journal Mobile Options
Table of Contents
Vol. 108, No. 4, 2002
Issue release date: November 2002
Acta Haematol 2002;108:237–245

Roles of Hematopoietic Transcription Factors GATA-1 and GATA-2 in the Development of Red Blood Cell Lineage

Ohneda K. · Yamamoto M.
Center for Tsukuba Advanced Research Alliance and Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Japan

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


The transcription factors GATA-1 and GATA-2 play key roles in gene regulation during erythropoiesis. Gene ablation studies in mouse revealed that GATA-2 is crucial for the maintenance and proliferation of immature hematopoietic progenitors, whereas GATA-1 is essential for the survival of erythroid progenitors as well as the terminal differentiation of erythroid cells. Both GATA-1 and GATA-2 are regulated in a cell-type-specific manner, their expression being strictly controlled during the development and differentiation of erythroid cells. Closer examination revealed a cross-regulatory mechanism by which GATA-1 can control the expression of GATA-2 and vice versa, possibly via essential GATA binding sites in their cis-acting elements. In addition, recent studies identified several human inherited hematopoietic disorders that are caused by mutations in cis-acting GATA binding motifs or mutations in GATA-1 itself.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Evans T, Felsenfeld G: The erythroid-specific transcription factor Eryf1: A new finger protein. Cell 1989;58:877–885.
  2. Tsai SF, Martin DI, Zon LI, D’Andrea AD, Wong GG, Orkin SH: Cloning of cDNA for the major DNA-binding protein of the erythroid lineage through expression in mammalian cells. Nature 1989;339:446–451.
  3. Yamamoto M, Ko LJ, Leonard MW, Beug H, Orkin SH, Engel JD: Activity and tissue-specific expression of the transcription factor NF-E1 multigene family. Genes Dev 1990;4:1650–1662.
  4. Ito E, Toki T, Ishihara H, Ohtani H, Gu L, Yokoyama M, Engel JD, Yamamoto M: Erythroid transcription factor GATA-1 is abundantly transcribed in mouse testis. Nature 1993;362:466–468.
  5. Hannon R, Evans T, Felsenfeld G, Gould H: Structure and promoter activity of the gene for the erythroid transcription factor GATA-1. Proc Natl Acad Sci USA 1991;88:3004–3008.
  6. Minegishi N, Ohta J, Suwabe N, Nakauchi H, Ishihara H, Hayashi N, Yamamoto M: Alternative promoters regulate transcription of the mouse GATA-2 gene. J Biol Chem 1998;273:3625–3634.
  7. Minegishi N, Ohta J, Yamagiwa H, Suzuki N, Kawauchi S, Zhou Y, Takahashi S, Hayashi N, Engel JD, Yamamoto M: The mouse GATA-2 gene is expressed in the para-aortic splanchnopleura and aorta-gonads and mesonephros region. Blood 1999;93:4196–4207.
  8. Pan X, Minegishi N, Harigae H, Yamagiwa H, Minegishi M, Akine Y, Yamamoto M: Identification of human GATA-2 gene distal IS exon and its expression in hematopoietic stem cell fractions. J Biochem 2000;127:105–112.
  9. Pevny L, Simon MC, Robertson E, Klein WH, Tsai SF, D’Agati V, Orkin SH, Costantini F: Erythroid differentiation in chimaeric mice blocked by a targeted mutation in the gene for transcription factor GATA-1. Nature 1991;349:257–260.
  10. Takahashi S, Onodera K, Motohashi H, Suwabe N, Hayashi N, Yanai N, Nabesima Y, Yamamoto M: Arrest in primitive erythroid cell development caused by promoter-specific disruption of the GATA-1 gene. J Biol Chem 1997;272:12611–12615.
  11. Fujiwara Y, Browne CP, Cunniff K, Goff SC, Orkin SH: Arrested development of embryonic red cell precursors in mouse embryos lacking transcription factor GATA-1. Proc Natl Acad Sci USA 1996;93:12355–12358.
  12. Takahashi S, Komeno T, Suwabe N, Yoh K, Nakajima O, Nishimura S, Kuroha T, Nagasawa T, Yamamoto M: Role of GATA-1 in proliferation and differentiation of definitive erythroid and megakaryocytic cells in vivo. Blood 1998;92:434–442.
  13. Harigae H, Takahashi S, Suwabe N, Ohtsu H, Gu L, Yang Z, Tsai FY, Kitamura Y, Engel JD, Yamamoto M: Differential roles of GATA-1 and GATA-2 in growth and differentiation of mast cells. Genes Cells 1998;3:39–50.
  14. Tsai FY, Keller G, Kuo FC, Weiss M, Chen J, Rosenblatt M, Alt FW, Orkin SH: An early haematopoietic defect in mice lacking the transcription factor GATA-2. Nature 1994;371:221–226.
  15. Suwabe N, Takahashi S, Nakano T, Yamamoto M: GATA-1 regulates growth and differentiation of definitive erythroid lineage cells during in vitro ES cell differentiation. Blood 1998;92:4108–4118.
  16. Briegel K, Lim KC, Plank C, Beug H, Engel JD, Zenke M: Ectopic expression of a conditional GATA-2/estrogen receptor chimera arrests erythroid differentiation in a hormone-dependent manner. Genes Dev 1993;7:1097–1109.
  17. Tsang AP, Fujiwara Y, Hom DB, Orkin SH: Failure of megakaryopoiesis and arrested erythropoiesis in mice lacking the GATA-1 transcriptional cofactor FOG. Genes Dev 1998;12:1176–1188.
  18. Merika M, Orkin SH: Functional synergy and physical interactions of the erythroid transcription factor GATA-1 with the Kruppel family protein Sp1 and EKLF. Mol Cell Biol 1995;15:2437–2447.
  19. Boyes J, Byfield P, Nakatani Y, Ogryzko V: Regulation of activity of the transcription factor GATA-1 by acetylation. Nature 1998;396:594–598.
  20. Onodera K, Takahashi S, Nishimura S, Ohta J, Motohashi H, Yomogida K, Hayashi N, Engel JD, Yamamoto M: GATA-1 transcription is controlled by distinct regulatory mechanisms during primitive and definitive erythropoiesis. Proc Natl Acad Sci USA 1997;94:4487–4492.
  21. Nishimura S, Takahashi S, Kuroha T, Suwabe N, Nagasawa T, Trainor C, Yamamoto M: A GATA box in the GATA-1 gene hematopoietic enhancer is a critical element in the network of GATA factors and sites that regulate this gene. Mol Cell Biol 2000;20:713–723.
  22. Takahashi S, Shimizu R, Suwabe N, Kuroha T, Yoh K, Ohta J, Nishimura S, Lim KC, Engel JD, Yamamoto M: GATA factor transgenes under GATA-1 locus control rescue germline GATA-1 mutant deficiencies. Blood 2000;96:910–916.
  23. Nichols KE, Crispino JD, Poncz M, White JG, Orkin SH, Maris JM, Weiss MJ: Familial dyserythropoietic anaemia and thrombocytopenia due to an inherited mutation in GATA1. Nat Genet 2000;24:266–270.
  24. Freson K, Devriendt K, Matthijs G, Van Hoof A, De Vos R, Thys C, Minner K, Hoylaerts MF, Vermylen J, Van Geet C: Platelet characteristics in patients with X-linked macrothrombocytopenia because of a novel GATA1 mutation. Blood 2001;98:85–92.
  25. Mehaffey MG, Newton AL, Gandhi MJ, Crossley M, Drachman JG, Freson K, Devriendt K, Matthijs G, Van Hoof A, De Vos R, Thys C, Minner K, Hoylaerts MF, Vermylen J, Van Geet C: X-linked thrombocytopenia caused by a novel mutation of GATA-1. Blood 2001;98:2681–2688.
  26. Wieser R, Volz A, Vinatzer U, Gardiner K, Jager U, Mitterbauer M, Ziegler A, Fonatsch C: Transcription factor GATA-2 gene is located near 3q21 breakpoints in myeloid leukemia. Biochem Biophys Res Commun 2000;273:239–245.
  27. Matsuda M, Sakamoto N, Fukumaki Y: Delta-thalassemia caused by disruption of the site for an erythroid-specific transcription factor, GATA-1, in the delta-globin gene promoter. Blood 1992;80:1347–1351.
  28. Manco L, Ribeiro ML, Maximo V, Almeida H, Costa A, Freitas O, Barbot J, Abade A, Tamagnini G: A new PKLR gene mutation in the R-type promoter region affects the gene transcription causing pyruvate kinase deficiency. Br J Haematol 2000;110:993–997.
  29. Solis C, Aizencang GI, Astrin KH, Bishop DF, Desnick RJ: Uroporphyrinogen III synthase erythroid promoter mutations in adjacent GATA1 and CP2 elements cause congenital erythropoietic porphyria. J Clin Invest 2001;107:753–762.
  30. Ludlow LB, Schick BP, Budarf ML, Driscoll DA, Zackai EH, Cohen A, Konkle BA: Identification of a mutation in a GATA binding site of the platelet glycoprotein Ib beta promoter resulting in the Bernard-Soulier syndrome. J Biol Chem 1996;271:22076–22080.
  31. Pevny L, Lin CS, D’Agati V, Simon MC, Orkin SH, Costantini F: Development of hematopoietic cells lacking transcription factor GATA-1. Development 1995;121:163–172.
  32. McDevitt MA, Shivdasani RA, Fujiwara Y, Yang H, Orkin SH: A ‘knockdown’ mutation created by cis-element gene targeting reveals the dependence of erythroid cell maturation on the level of transcription factor GATA-1. Proc Natl Acad Sci USA 1997;94:6781–6785.
  33. Pandolfi PP, Roth ME, Karis A, Leonard MW, Dzierzak E, Grosveld FG, Engel JD, Lindenbaum MH: Targeted disruption of the GATA3 gene causes severe abnormalities in the nervous system and in fetal liver haematopoiesis. Nat Genet 1995;11:40–44.
  34. Lim KC, Lakshmanan G, Crawford SE, Gu Y, Grosveld F, Engel JD: Gata3 loss leads to embryonic lethality due to noradrenaline deficiency of the sympathetic nervous system. Nat Genet 2000;25:209–212.
  35. Moi P, Loudianos G, Lavinha J, Murra S, Cossu P, Casu R, Oggiano L, Longinotti M, Cao A, Pirastu M: Delta-thalassemia due to a mutation in an erythroid-specific binding protein sequence 3′ to the delta-globin gene. Blood 1992;79:512–516.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50