Molecular Evolution of the GATA Family of Transcription Factors: Conservation Within the DNA-Binding Domain

Lowry, Jason A.; Atchley, William R.

doi:10.1007/s002399910012

Cited by 278 publications

(248 citation statements)

References 62 publications

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“…GATA3 is one of six members of a family of transcription factors that bind the consensus motif A/TGATAA/G and which regulates critical steps of differentiation during embryonic development [1]. GATA3 is located at chromosome 10p15 [2].…”

Section: Introductionmentioning

confidence: 99%

“…GATA 1, 2 and 3 are critically involved in myeloerythropoiesis whereas GATA 4, 5 and 6 are implicated in cardiac and intestinal development [3]. The binding element comprises two C4 zinc finger motifs shared with the steroid hormone receptor super family, and is highly conserved among different vertebrate and invertebrate species [1]. GATA3 regulates lineage determination of many cell types.…”

Section: Introductionmentioning

confidence: 99%

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The significance of GATA3 expression in breast cancer: a 10-year follow-up study

Ciocca¹,

Daskalakis²,

Ciocca³

et al. 2009

Human Pathology

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The significance of GATA3 expression in breast cancer: a 10-year follow-up study

Ciocca¹,

Daskalakis²,

Ciocca³

et al. 2009

Human Pathology

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“…The GATA family of transcription factors consists of six members that have two highly conserved zinc-finger domains and recognize a consensus DNA-binding motif of (A/T)/GATA/(A/G) (Lowry and Atchley, 2000). They regulate biological functions, including organogenesis, differentiation, proliferation and apoptosis (Perlman et al, 1998;Koutsourakis et al, 1999;Lowry and Atchley, 2000;Cantor and Orkin, 2002;Wada et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…They regulate biological functions, including organogenesis, differentiation, proliferation and apoptosis (Perlman et al, 1998;Koutsourakis et al, 1999;Lowry and Atchley, 2000;Cantor and Orkin, 2002;Wada et al, 2002). GATA-1, -2 and -3 are important for the development of the nervous system and hematopoietic cell lineages (Cantor and Orkin, 2002;Patient and McGhee, 2002).…”

Section: Introductionmentioning

confidence: 99%

GATA4 is a regulator of astrocyte cell proliferation and apoptosis in the human and murine central nervous system

et al. 2009

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The GATA transcription factors consist of six family members, which bind to the consensus DNA-binding element, W-GATA-R, and are poorly characterized in the central nervous system (CNS). Using retroviral gene trapping on transgenic mouse glioma models, we identified GATA6 to be a novel tumor suppressor gene in glioblastoma multiforme. We now show GATA4, a family member of GATA6, to be expressed in the neurons and glia of normal murine and human embryonic and adult CNS. Silencing GATA4 in normal astrocytes did not alter their growth properties. In contrast, knockdown of Gata4 in p53 null non-transformed murine astrocytes induced transformation, with increased proliferation and resistance to chemotherapy or radiation-induced apoptosis. Furthermore, GATA4 expression was lost in a panel of human malignant astrocytoma cell lines. GATA4 overexpression in normal human and murine astrocytes resulted in a cell cycle block in G1 phase, with increased apoptosis. Mechanistically, GATA4 was a transcriptional inducer of the cyclin-dependent kinase inhibitor, p15INK4B, leading to the attenuation of cyclin D1. GATA4 expression was also induced by transforming growth factor-b, leading to the inhibition of astrocyte proliferation. Collectively, we show that GATA4 is expressed in the embryonic and adult CNS and acts as a negative regulator of astrocyte proliferation and growth.

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“…An evolutionary analysis of the entire family indicates that only the C-terminal zinc finger and corresponding C-terminal basic arm are conserved (43). Furthermore, a single duplication event that apparently conserves the core finger GAT binding specificity is responsible for the GATA proteins with two zinc fingers.…”

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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Molecular Evolution of the GATA Family of Transcription Factors: Conservation Within the DNA-Binding Domain

Cited by 278 publications

References 62 publications

The significance of GATA3 expression in breast cancer: a 10-year follow-up study

The significance of GATA3 expression in breast cancer: a 10-year follow-up study

GATA4 is a regulator of astrocyte cell proliferation and apoptosis in the human and murine central nervous system

Determinants of GATA-1 Binding to DNA

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