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NF-ATc isoforms are differentially expressed and regulated in murine T and mast cells
M A Sherman1, D R Powell, D L Weiss
1Department of Experimental Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Abstract:
NF of activated T cells (NF-AT) denotes a family of transcription factors that regulate the activation-dependent expression of many immunologically important proteins. At least four distinct genes encode the various family members, and several isoforms of these have been identified as well. The overlapping expression patterns and similar in vitro binding and trans-activation activities on various promoter elements of NF-AT-regulated genes suggest some redundancy in the function of these proteins. However, the phenotypic analysis of NF-AT-deficient mice supports the idea that there are tissue- and gene-specific functions as well. In this study we have characterized the expression of NF-AT cDNAs in murine mast cells. The majority of clones identified correspond to two NF-ATc isoforms that differ only in their amino-terminal sequence. Despite minimal discrepancies in the coding region, there are striking tissue- and cell type-specific differences in isoform expression patterns. Detection of NF-ATc.alpha mRNA is strictly dependent on cell activation signals in both T and mast cell lines. In contrast, the beta isoform is expressed at very low constitutive levels in both cell types but is only up-regulated in response to mast cell activation signals delivered through the FcepsilonRI or via calcium ionophores. These results demonstrate another level of regulation within the NF-AT family that can contribute to cell type-specific gene expression.
Insights
Nuclear Factor of activated T cells (NF-AT) family members exhibit cell-specific expression patterns. This study reveals distinct isoform regulation in mast cells, highlighting NF-ATc.alpha and NF-ATc.beta differential responses to activation signals.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Nuclear Factor of activated T cells (NF-AT) are transcription factors crucial for immune responses.
- Multiple NF-AT genes and isoforms exist, suggesting potential functional redundancy and specificity.
- Previous studies indicated tissue-specific roles for NF-AT proteins.
Purpose of the Study:
- To investigate the expression patterns of NF-ATc isoforms in murine mast cells.
- To understand the regulatory mechanisms controlling NF-AT isoform expression in response to activation signals.
- To elucidate the contribution of NF-AT isoform diversity to cell type-specific gene expression.
Main Methods:
- Characterization of NF-AT cDNA expression in murine mast cells.
- Analysis of NF-ATc.alpha and NF-ATc.beta mRNA expression levels.
- Assessment of isoform expression in response to mast cell activation via FcepsilonRI and calcium ionophores.
Main Results:
- Two major NF-ATc isoforms, differing in their amino-terminal sequences, were identified.
- NF-ATc.alpha mRNA expression was strictly dependent on cell activation in both T and mast cells.
- NF-ATc.beta was constitutively expressed at low levels but significantly upregulated upon mast cell activation.
Conclusions:
- NF-AT isoform expression is tightly regulated in a cell type- and activation-dependent manner.
- Differential regulation of NF-ATc.alpha and NF-ATc.beta provides a mechanism for cell-specific gene expression.
- These findings add another layer of complexity to the functional diversification of the NF-AT family.
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