Authors:
Cruickshank MN, Dods J, Taylor RL, Karimi M, Fenwick EJ, Quail EA, et al.
Authors notes:
Int J Biochem Cell Biol. 2015;64:107-19.
Keywords:
B cells, Gene regulation, Human Transcription factors
Abstract:
Complement receptor 2 (CR2/CD21) plays an important role in the generation of normal B cell immune responses.
As transcription appears to be the prime mechanism via which surface CR2/CD21 expression is controlled, understanding transcriptional regulation of this gene will have broader implications to B cell biology.
Here we report opposing, cell-context specific control of CR2/CD21 promoter activity by tandem E-box elements, spaced 22 bp apart and within 70 bp of the transcription initiation site.
We have identified E2A and USF transcription factors as binding to the distal and proximal E-box sites respectively in CR2-positive B-cells, at a site that is hypersensitive to restriction enzyme digestion compared to non-expressing K562 cells.
However, additional unidentified proteins have also been found to bind these functionally important elements.
By utilizing a proteomics approach we have identified a repressor protein, RP58, binding the distal E-box motif.
Co-transfection experiments using RP58 overexpression constructs demonstrated a specific 10-fold repression of CR2/CD21 transcriptional activity mediated through the distal E-box repressor element.
Taken together, our results indicate that repression of the CR2/CD21 promoter can occur through one of the E-box motifs via recruitment of RP58 and other factors to bring about a silenced chromatin context within CR2/CD21 non-expressing cells