Familial dyserythropoietic anaemia and thrombocytopenia due to an inherited mutation in GATA1

Nichols, Kim E.; Crispino, John D.; Poncz, Mortimer; White, James G.; Orkin, Stuart H.; Maris, John M.; Weiss, Mitchell J.

doi:10.1038/73480

Cited by 467 publications

(424 citation statements)

References 26 publications

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“…Cooperation between GATA-1 and FOG-1 is required for normal erythropoiesis (Crispino et al, 1999), and within the megakaryocyte lineage FOG-1 acts with either GATA-1 or GATA-2 to direct differentiation of early precursors (Nichols et al, 2000;Chang et al, 2002;Cantor et al, 2002;Garriga-Canut and Orkin, 2004). FOG-1 is co-expressed with GATA-3 in naive T-cells and may repress T helper 2 cell development (Zhou et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

GATA‐4:FOG interactions regulate gastric epithelial development in the mouse

Jacobsen¹,

Mannisto²,

Porter-Tinge³

et al. 2005

Developmental Dynamics

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Transcription factor GATA-4 is a key participant in cytodifferentiation of the mouse hindstomach. Here we show that GATA-4 cooperates with a Friend-of-GATA (FOG) cofactor to direct gene expression in this segment of gut. Immunohistochemical staining revealed that GATA-4 and FOG-1 are co-expressed in hindstomach epithelial cells from embryonic days (E) 11.5 to 18.5. The other member of the mammalian FOG family, FOG-2, was not detected in gastric epithelium. To show that GATA-4:FOG interactions influence stomach development, we analyzed Gata4 ki/ki mice, which express a mutant GATA-4 that cannot bind FOG cofactors. Sonic Hedgehog, an endoderm-derived signaling molecule normally down-regulated in the distal stomach, was over-expressed in hindstomach epithelium of E11.5 Gata4 ki/ki mice, and there was a concomitant decrease in fibroblast growth factor-10 in adjacent mesenchyme. We conclude that functional interaction between GATA-4 and a member of the FOG family, presumably FOG-1, is required for proper epithelial-mesenchymal signaling in the developing stomach. Developmental Dynamics 234:355-362, 2005.

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Section: Discussionmentioning

confidence: 99%

GATA‐4:FOG interactions regulate gastric epithelial development in the mouse

Jacobsen¹,

Mannisto²,

Porter-Tinge³

et al. 2005

Developmental Dynamics

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“…37 PCR products were prepared with the QIAquick PCR purification kit (Qiagen, GmbH, Germany) and sequenced directly using the BigDye terminator system and the ABI 310 analyzer (Applied Biosystem).…”

Section: Gata-1 Sequencingmentioning

confidence: 99%

Abnormalities of GATA-1 in Megakaryocytes from Patients with Idiopathic Myelofibrosis

Vannucchi¹,

Pancrazzi²,

Guglielmelli³

et al. 2005

The American Journal of Pathology

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The abnormal megakaryocytopoiesis associated with idiopathic myelofibrosis (IM) plays a role in its pathogenesis. Because mice with defective expression of transcription factor GATA-1 (GATA-1 low mutants) eventually develop myelofibrosis, we investigated the occurrence of GATA-1 abnormalities in IM patients. CD34 ؉ cells were purified from 12 IM patients and 8 controls; erythroblasts and megakaryocytes were then obtained from unilineage cultures of CD34 ؉ cells. Purified CD61 ؉ , GPA ؉ , and CD34 ؉ cells from IM patients contained levels of GATA-1, GATA-2, and FOG-1 mRNA, as well as of GATA-2 protein, that were similar to controls. In contrast, CD61 ؉ cells from IM patients contained significantly reduced GATA-1 protein. Furthermore, 45% of megakaryocytes in biopsies from IM patients did not stain with anti-GATA-1 antibody, as compared to controls (2%), essential thrombocythemia (4%), or polycythemia vera (11%) patients. Abnormalities in immunoreactivity for FOG-1 were not found, and no mutations in GATA-1 coding sequences were found. The presence of GATA-1 neg megakaryocytes in bone marrow biopsies was independent of the Val617Phe JAK2 mutation, making it unlikely that a downstream functional relationship exists. We conclude that megakaryocytes from IM patients have reduced GATA-1 content, possibly contributing to disease pathogenesis as in the GATA-1 low mice and also representing a novel IM-associated marker. (Am J Pathol 2005, 167:849 -858)

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“…Rescue experiments with proteins containing similar mutations in the N-terminal zinc finger result in live mice that are severely impaired in definitive erythropoiesis (27). Whereas some of the observed phenotype is because of the inability of these mutant proteins to interact with the critical cofactor FOG (28,32), N-terminal zinc finger mutants that retain the ability to interact with FOG but have impaired DNA binding also show defects in erythropoiesis in transgenic rescue FIG. 5.…”

Section: Discussionmentioning

confidence: 99%

Determinants of GATA-1 Binding to DNA

Ghirlando

Trainor

2003

Journal of Biological Chemistry

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Mammalian GATA transcription factors are expressed in various tissues in a temporally regulated manner. The prototypic member, GATA-1, is required for normal erythroid, megakaryocytic, and mast cell development. This family of DNA-binding proteins recognizes a consensus (A/T)GATA(A/G) motif and possesses homologous DNA binding domains consisting of two zinc fingers. The C-terminal finger of GATA-1 recognizes the consensus motif with nanomolar affinities, whereas the N-terminal finger shows a binding preference for a GATC motif, albeit with much reduced affinity (K d Ϸ M). The Nterminal finger of GATA-2 also shows a preference for an AGATCT binding site, with an increased affinity attributed to N-and C-terminal flanking basic residues (K d Ϸ nM). To understand the differences in the binding specificities of the N-and C-terminal zinc fingers of GATA-1, we have constructed a series of swapped domain peptides. We show that the specificity for AGATAA over AGATCT arises from the C-terminal non-finger basic domain. Thus, the N-terminal finger binds preferentially to AGATAA once appended to the C-terminal arm of the C-terminal finger. We further show that this specificity arises from the highly conserved QTRNRK residues. The converse is, however, untrue in the case of the C-terminal finger; swapping of QTRNRK with the corresponding LVSKRA does not switch the DNA binding specificity from AGATAA to AGATCT. These results highlight the important role of residues adjacent to the CXXCX 17 CNAC zinc finger motif (i.e. non-finger residues) in the specific recognition of DNA residues.DNA binding zinc fingers of the form CXXCX 17 CNAC characterize the GATA family of transcription factors. GATA-1, the original member of the family possesses two such zinc fingers (1, 2). The C-terminal finger and flanking basic arm are both necessary and sufficient for binding to the GATA recognition sequence, (A/T)GATA(A/G) (3, 4). Even though the single Nterminal finger does not bind DNA independently with high affinity, it does stabilize GATA-1 interactions with some sites crucial for gene expression (3,(5)(6)(7)(8). Recent reports, however, indicate that the N-terminal finger binds DNA with an affinity much lower than that observed for the C-terminal finger with binding occurring preferentially to GATC motifs (9). Despite the similarities between the C-and N-terminal fingers (Fig. 1, peptides CC11 and NN4, respectively), the N-terminal finger does not recognize the AGATAA consensus motif, indicating that the flanking or poorly conserved linker residues may play a key role in DNA recognition. A role for the flanking residues has been pointed out in the case of the N-terminal finger of GATA-2 (10). Like the N-terminal finger of GATA-1, this homologous finger shows a binding preference for GATC motifs. However, because of the additional basic region at the N terminus a higher binding affinity has been reported for this finger.Solution NMR studies of the complex formed between the C-terminal finger of cGATA-1 and the AGATAA DNA sequence highlight t...

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Familial dyserythropoietic anaemia and thrombocytopenia due to an inherited mutation in GATA1

Cited by 467 publications

References 26 publications

GATA‐4:FOG interactions regulate gastric epithelial development in the mouse

GATA‐4:FOG interactions regulate gastric epithelial development in the mouse

Abnormalities of GATA-1 in Megakaryocytes from Patients with Idiopathic Myelofibrosis

Determinants of GATA-1 Binding to DNA

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