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Genes newly identified as regulated by glucocorticoids in murine thymocytes
G Baughman1, M T Harrigan, N F Campbell
1Regulatory Biology Laboratory, Salk Institute for Biological Studies, San Diego, California 92186-5800.
Abstract:
Glucocorticoids induce dramatic biochemical and morphological changes in lymphocytes through an unknown process that requires RNA and protein synthesis. In order to identify genes involved in this response, we previously isolated 11 cDNA clones from the murine WEHI-7TG thymoma cell line that correspond to mRNAs induced by glucocorticoids. We now report the isolation of two new cDNA clones whose gene expression is regulated by glucocorticoids in WEHI-7TG cells. We further characterize the two new cDNA clones, as well as those described previously, by examining the response of each of the corresponding mRNAs to glucocorticoids in murine thymocytes. With the exception of two, all cDNAs correspond to genes that are induced by glucocorticoids in murine thymocytes within 4 h of treatment. We previously identified two of the cDNAs as the mouse VL30 retrovirus-like element and the mouse homolog of chondroitin sulfate proteoglycan core protein. We have now identified four additional cDNA clones that correspond to the genes for calmodulin, mitochondrial phosphate carrier protein, immunoglobulin (Ig)-related glycoprotein (GP-70), and the 70 kilodalton autoantigen for Lupus and Graves diseases. Two other cDNA clones represent previously undescribed genes: one shares a high similarity to known sequences for the family of G-protein-coupled receptors and the other to a human placental-specific protein, PP11. Another cDNA appears to contain sequences for an unknown gene and the remnants of a mouse transposon. ETn. The remaining clones represent new, unidentified genes induced by glucocorticoids in murine thymocytes and in the WEHI-7TG cell line.
Insights
Glucocorticoids rapidly induce gene expression changes in lymphocytes. Researchers identified new genes, including those for calmodulin and G-protein-coupled receptors, involved in this glucocorticoid response.
Area of Science:
- Molecular Biology
- Immunology
- Genetics
Background:
- Glucocorticoids trigger significant biochemical and morphological alterations in lymphocytes.
- This process necessitates RNA and protein synthesis but the underlying genes were largely unknown.
Purpose of the Study:
- To identify genes regulated by glucocorticoids in lymphocytes.
- To characterize novel cDNA clones responsive to glucocorticoid treatment.
Main Methods:
- Isolation of cDNA clones from murine WEHI-7TG thymoma cells.
- Analysis of mRNA expression in response to glucocorticoids in WEHI-7TG cells and murine thymocytes.
- Sequencing and identification of isolated cDNA clones.
Main Results:
- Two new glucocorticoid-regulated cDNA clones were identified in WEHI-7TG cells.
- Most identified cDNAs (11 previously, 2 new) were induced by glucocorticoids in murine thymocytes within 4 hours.
- Identified genes include those for calmodulin, mitochondrial phosphate carrier protein, immunoglobulin-related glycoprotein (GP-70), and a 70 kDa autoantigen.
- Novel genes identified include a G-protein-coupled receptor homolog and a human placental protein (PP11) homolog.
- Other clones represent unidentified genes and remnants of a mouse transposon (ETn).
Conclusions:
- Glucocorticoids induce a rapid and diverse set of gene expression changes in lymphocytes.
- The identified genes play roles in various cellular functions, including signaling, metabolism, and immune responses.
- This study expands the understanding of the molecular mechanisms underlying glucocorticoid action in lymphocytes.