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The human beta 2 integrin CD18 promoter consists of two inverted Ets cis elements
E P Böttinger1, C S Shelley, O C Farokhzad
1Department of Medicine, Harvard Medical School, Charlestown, Massachusetts.
Molecular and Cellular Biology
|April 1, 1994
Summary
Researchers identified the minimal CD18 promoter, crucial for myeloid and lymphoid cell expression. This region, driven by Ets factors like GABP and PU.1, regulates gene activity without traditional promoter elements.
Area of Science:
- Molecular Biology
- Gene Regulation
- Hematopoiesis
Background:
- CD18 is essential for myeloid and lymphoid cell function.
- Understanding its promoter is key to controlling gene expression in these cells.
Purpose of the Study:
- To define the minimal promoter region responsible for CD18 gene expression.
- To identify the transcription factors that regulate this minimal promoter.
Main Methods:
- Deletion construct analysis of the CD18 gene promoter region.
- Luciferase reporter gene assays in hematopoietic cell lines.
- DNase I footprinting and gel retardation assays to identify protein-DNA interactions.
Main Results:
- A 321 bp region (-302 to +19) was sufficient for cell-restricted and inducible CD18 expression.
- Two key DNA binding sites (box A and box B) were identified within this minimal promoter.
- Ets family proteins, including GABP and PU.1, were found to bind these sites and are essential for transcriptional activation.
Conclusions:
- The minimal CD18 promoter relies on Ets transcription factors for regulation.
- This promoter lacks canonical elements like TATA and CAAT boxes.
- It represents a novel class of promoters where Ets factor binding is sufficient for activation.