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Published on: February 28, 2019
Activating transcription factor/cAMP response element binding protein family member regulated transcription of CD1A
Angela Colmone1, Sha Li, Chyung-Ru Wang
1Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
Insights
Researchers identified a key DNA region controlling CD1A gene expression. Activating ATF/CREB transcription factors decrease CD1A transcription, while reduced ATF-2 increases it, revealing insights into immune cell regulation.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- CD1a is an antigen-presenting molecule with a specific expression pattern on cortical thymocytes and antigen-presenting cells (APCs).
- Alterations in CD1a expression are linked to autoimmune diseases, infections, and tumors, highlighting the need to understand its regulation.
Purpose of the Study:
- To characterize the transcriptional regulation of CD1A.
- To identify the minimal promoter region and key regulatory elements involved in CD1A gene expression.
Main Methods:
- Bioinformatic analysis to identify potential transcription factor binding sites within the CD1A promoter region.
- Deletion and site-specific mutant analysis to determine the functional significance of identified elements.
- In vitro and in vivo assays to assess transcription factor binding and activity.
Main Results:
- A minimal proximal promoter region essential for CD1A transcription was identified.
- A cAMP response element (CRE) located 965 bp upstream of the translation start site was found to be critical.
- CREB-1 and ATF-2 were shown to bind this CRE site.
- Activation of ATF/CREB family members decreased CD1A transcription, whereas decreased ATF-2 expression led to increased CD1A RNA levels.
Conclusions:
- ATF/CREB family members play a significant role in regulating CD1A expression.
- These findings suggest a mechanism for controlling CD1A transcription in immune cells, potentially impacting disease states.
Abstract:
CD1a has a unique expression pattern among Ag-presenting molecules, expressed specifically on cortical thymocytes and APCs. As autoimmune disease, infection, and tumors can all result in alteration of CD1a expression, we are attempting to characterize the transcriptional regulation, and thus shed some light on specific expression, of CD1A. In this study, we have identified a minimal proximal promoter region required for CD1A transcription. Computer searches within this region identified numerous potential binding sites for lymphoid-specific transcription factors, including the ETS transcription factors, C/EBP, GATA, and CREB. Deletion and site-specific mutant analysis revealed a critical role of a potential cAMP response element (CRE) 965 bp upstream of the CD1A translation start site. Two activating transcription factor (ATF)/CREB family members, CREB-1 and ATF-2, are able to bind this site in vitro and in vivo. Notably, activation of ATF/CREB family members decreases CD1A transcription, while decrease in ATF-2 expression results in increased CD1A RNA level. The fact that these factors also bind the CD1A promoter in human monocytes strongly suggests a role for ATF/CREB family members in regulation of CD1A expression.
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