Interaction of the erythroid transcription factor cGATA-1 with a critical auto-regulatory element

Schwartzbauer, Gary; Schlesinger, Kurt; Evans, Todd

doi:10.1093/nar/20.17.4429

Cited by 40 publications

(27 citation statements)

References 31 publications

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“…That the nucleotides several positions away from the central GAT can affect GATA factor function through that site is evidenced by recent studies of the cGATA-1 promoter region. A deletion of the nucleotide at the -3 position of the GATA site at -139 of the promoter results in an increased dissociation rate of DNA-protein complex formation and a 30% diminution of promoter activity (36).…”

Section: Discussionmentioning

confidence: 99%

“…Confirmation of the necessity of the first three nucleotides was demonstrated by methylation interference experiments with human GATA-1, suggesting that the most critical contact point identified in the recognition sequence was the G (46); subsequent studies with cGATA-1 confirmed this conclusion (36). Other experiments showed that mutation of the first A or T resulted in an 80-or 60-fold-lower affinity of factor binding, respectively, while mutation of the second A led to only a 20-fold decrease in affinity (29), consistent with the GAT consensus derivation.…”

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confidence: 86%

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DNA-binding specificities of the GATA transcription factor family.

Ko¹,

Engel²

1993

Mol. Cell. Biol.

495

374

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Members of the GATA family of transcription factors, which are related by a high degree of amino acid sequence identity within their zinc finger DNA-binding domains, each show distinct but overlapping patterns of tissue-restricted expression. Although GATA-1, -2, and -3 have been shown to recognize a consensus sequence derived from regulatory elements in erythroid cell-specific genes, WGATAR (in which W indicates A/T and R indicates A/G), the potential for more subtle differences in the binding preferences of each factor has not been previously addressed. By employing a binding selection and polymerase chain reaction amplification scheme with randomized oligonucleotides, we have determined the binding-site specificities of bacterially expressed chicken GATA-1, -2, and -3 transcription factors. Whereas all three GATA factors bind an AGATAA erythroid consensus motif with high affinity, a second, alternative consensus DNA sequence, AGATCTTA, is also recognized well by GATA-2 and GATA-3 but only poorly by GATA-1. These studies suggest that all three GATA factors are capable of mediating transcriptional effects via a common erythroid consensus DNA-binding motif. Furthermore, GATA-2 and GATA-3, because of their distinct expression patterns and broader DNA recognition properties, may be involved in additional regulatory processes beyond those of GATA-1. The definition of an alternative GATA-2-GATA-3 consensus sequence may facilitate the identification of new target genes in the further elucidation of the roles that these transcription factors play during development.Many transcription factors have been found to be members of highly related multifactor families, and thus their specificity of action must be addressed in order to ascertain their respective functions. Consequently, it is critical to determine which factor, from an array of factors with closely related DNA-binding motifs, acts upon a particular recognition site from a variety of sites with similar sequences. Equally important is the elucidation of the means by which this discrimination is achieved; a variety of mechanisms by which related transcription factors are targeted to distinct regulatory elements have been discovered. Differences in DNA-binding properties direct the zinc finger estrogen and progesterone receptors to their appropriate targets (7,44), as is the case with the Antennapedia-related homeodomain proteins Ultrabithorax and Deforned (8,9). The related retinoic acid, thyroid hormone, and vitamin D receptors exemplify a unique solution to the problem of differential target recognition by discriminating between the spacing and orientation of closely related binding sites of these obligate dimers (27,45

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 86%

DNA-binding specificities of the GATA transcription factor family.

Ko¹,

Engel²

1993

Mol. Cell. Biol.

495

374

View full text Add to dashboard Cite

show abstract

“…Given the established roles of GATA factors in hematopoietic gene regulation, it seemed likely that the GATA boxes in the 5 0 UTR are critical for Hemgn transactivation. Since previous studies have shown that the G in the GATA core sequence is critical for the binding of GATA factors, [22][23][24] the sequence was mutated to a/cATA to abolish GATA binding activity. [17][18][19] Indeed, in our analysis mutation of the GATA box1 or GATA box2 sites suppressed promoter activity in K562 cells by about 95 and 90%, respectively (Figure 4b).…”

Section: Isolating Mouse Hemgn Promotersmentioning

confidence: 99%

The GATA site-dependent hemogen promoter is transcriptionally regulated by GATA1 in hematopoietic and leukemia cells

Yang

Wan

et al. 2006

Leukemia

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Hemgn (a gene symbol for hemogen in mouse, EDAG in human and RP59 in rat) encodes a nuclear protein that is highly expressed in hematopoietic tissues and acute leukemia. To characterize its regulatory mechanisms, we examined the activities of a Hemgn promoter containing 2975 bp of 5 0 flanking sequence and 196 bp of 5 0 untranslated region (5 0 UTR) sequence both in vitro and in vivo: this promoter is preferentially activated in a hematopoietic cell line, not in nonhematopoietic cell lines, and is sufficient to drive the transcription of a lacZ transgene in hematopoietic tissues in transgenic mice. Mutagenesis analyses showed that the 5 0 UTR including two highly conserved GATA boxes is critical for the promoter activity. GATA1, not GATA2, binds to the GATA binding sites and transactivates the Hemgn promoter in a dose-dependent manner. Furthermore, the expression of human hemogen (EDAG) transcripts were closely correlated with levels of GATA1 transcripts in primary acute myeloid leukemia specimens. This study suggests that the Hemgn promoter contains critical regulatory elements for its transcription in hematopoietic tissues and Hemgn is a direct target of GATA1 in leukemia cells.

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“…5 The primers used in this study were human GATA-1 (forward We detected GATA-1 in only five of the 45 MDS patients (11.1%) and GATA-2 in 40 patients (88.9%) ( Figure 1). Since GATA-1 expression may be auto-regulated or controlled by other GATA family members including GATA-2, 11,12 we attempted to divide the MDS patients into one of the following four groups according to the expression of GATA-1 and GATA-2 genes; GATA-…”

mentioning

confidence: 99%

GATA-1 and GATA-2 gene expression is related to the severity of dysplasia in myelodysplastic syndrome

Harun

et al. 2002

Leukemia

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Interaction of the erythroid transcription factor cGATA-1 with a critical auto-regulatory element

Cited by 40 publications

References 31 publications

DNA-binding specificities of the GATA transcription factor family.

DNA-binding specificities of the GATA transcription factor family.

The GATA site-dependent hemogen promoter is transcriptionally regulated by GATA1 in hematopoietic and leukemia cells

GATA-1 and GATA-2 gene expression is related to the severity of dysplasia in myelodysplastic syndrome

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