Temporal and Spatial Control of Murine GATA-3 Transcription by Promoter-Proximal Regulatory Elements

The GATA family of transcription factors regulates development of multiple tissues. Several GATA factors have two promoters directing distinct tissue-specific expression. Although GATA-3 acts in both neuronal and thymocyte development, no alternative promoter usage has been reported. We examined various cell types and tissues for potential alternative GATA-3 transcripts and identified an alternative transcript directed by a promoter located 10 kb upstream of the recognized promoter. Sequences within this promoter and alternative first exon are highly conserved between mouse and human genomes. This new promoter is expressed selectively in the brain but is essentially undetectable in the thymus. In contrast, the recognized promoter is selectively expressed in the thymus but not in the brain. We also observed a gradual increase in expression from this new promoter during Th2 development. These results indicate that similar to other GATA factors, the GATA-3 gene can be controlled by two promoters that may direct lineage- and tissue-specific expression.

Section: Figurementioning

confidence: 93%

Cutting Edge: Identification of an Alternative GATA-3 Promoter Directing Tissue-Specific Gene Expression in Mouse and Human

Asnagli

Afkarian

Murphy

2002

“…3 presents a side-by-side analysis of two GATA family members and two Pax family members in adult lymphoid (Ig and/or TCR ϩ ) and nonlymphoid tissues of the mouse and skate, respectively. GATA-3 in the mouse is expressed in several nonhemopoietic tissues in addition to T cells, under control of distinct sets of cis-regulatory sequences (40,41). Thus, GATA-3 expression in the skate would not be expected to be confined solely to TCR ϩ cells.…”

Section: Conservation Of Lymphoid Expression Patterns In Skate Ortholmentioning

confidence: 99%

Evolutionary Origins of Lymphocytes: Ensembles of T Cell and B Cell Transcriptional Regulators in a Cartilaginous Fish

Anderson

Pant

Miracle

et al. 2004

The evolutionary origins of lymphocytes can be traced by phylogenetic comparisons of key features. Homologs of rearranging TCR and Ig (B cell receptor) genes are present in jawed vertebrates, but have not been identified in other animal groups. In contrast, most of the transcription factors that are essential for the development of mammalian T and B lymphocytes belong to multigene families that are represented by members in the majority of the metazoans, providing a potential bridge to prevertebrate ancestral roles. This work investigates the structure and regulation of homologs of specific transcription factors known to regulate mammalian T and B cell development in a representative of the earliest diverging jawed vertebrates, the clearnose skate (Raja eglanteria). Skate orthologs of mammalian GATA-3, GATA-1, EBF-1, Pax-5, Pax-6, Runx2, and Runx3 have been characterized. GATA-3, Pax-5, Runx3, EBF-1, Spi-C, and most members of the Ikaros family are shown throughout ontogeny to be 1) coregulated with TCR or Ig expression, and 2) coexpressed with each other in combinations that for the most part correspond to known mouse T and B cell patterns, supporting conservation of function. These results indicate that multiple components of the gene regulatory networks that operate in mammalian T cell and B cell development were present in the common ancestor of the mammals and the cartilaginous fish. However, certain factors relevant to the B lineage differ in their tissue-specific expression patterns from their mouse counterparts, suggesting expanded or divergent B lineage characteristics or tissue specificity in these animals.

“…Previously, it was reported that an ϳ2.5-kb genomic fragment, encompassing the murine GATA-3 promoter, its upstream region, the first exon, the first intron, and the untranslated part of the second exon, was sufficient to confer T cell specificity in vitro (8,9). In addition, the 3Ј end of the first intron of the human GATA-3 gene was found to be critical for the activity of a human GATA-3 promoter (10).…”

Section: Identification Of a T Cell-specific Regulatory Region In Thementioning

confidence: 99%

“…An ϳ2.5-kb genomic fragment encompassing several of the DNase I hypersensitivity sites is sufficient to support the expression of a reporter gene in a T cellspecific manner in vitro (8,9). A recent report showed that the T cell specificity of the human GATA-3 gene might be regulated by an upstream silencer and a positive cis-acting element, which is located in the 3Ј end of the first intron, however, neither of the regulatory elements was cell type-specific (10,11).…”

mentioning

confidence: 99%

Transcriptional Regulation of GATA-3 by an Intronic Regulatory Region and Fetal Liver Zinc Finger Protein 1

Hwang

Choi

2002

GATA-3 is a T cell-specific transcription factor and is essential for the development of the T cell lineage. The transcriptional regulation of GATA-3, however, remains elusive. In this study, we report the identification of a regulatory region located within the first intron of the murine GATA-3 gene. The intronic regulatory region contains both a positive and a negative cis-acting element but, as a whole, serves as a potent T cell-specific enhancer and is essential for the promoter activity in vitro. By using yeast one-hybrid screening, we discovered that fetal liver zinc finger protein 1 (Fliz1) could bind specifically to the negative cis-acting element, the sequence of which is conserved between the mouse and human GATA-3 genes. More importantly, overexpression of Fliz1 repressed the expression of GATA-3 in vivo and in vitro. Our data suggest that the expression of GATA-3 might be partly regulated by the intronic regulatory region and Fliz1 in a developmental stage-specific fashion.