CD21/CR2 as a possible Myc target gene in hematopoietic cell lines

Abstract

c-Myc is a transcription factor which belongs to the family of basic-helix/loop/helix-leucine zipper proteins. It is found deregulated in more than 50% of human tumors, including Burkitt lymphoma, a human B-cell tumor, where Myc is chromosomally translocated. There is an African epidemic version of Burkitt lymphoma associated with the infection of Epstein-Barr virus (EBV). CD21/CR2 is the co-receptor of B-cell receptor (BCR) that serves as receptor for this virus. We explored whether CR2 could be a potential Myc target gene, since previous results in our laboratory showed that CR2 and Myc were correlated. We have used several hematopoietic cell lines (Raji and K562) in which we have measured CR2 mRNA levels by qPCR upon different conditions of Myc expression. Our results indicate that Myc overexpression in K562 cells results in CR2 overexpression and this effect is reproduced in the absence of protein synthesis. Moreover, in Burkitt cells, inhibition of Myc through the drug JQ1 (which impairs Myc transcription) resulted in CR2 mRNA decrease. The bioinformatic analysis of the ChIP-seq data of the ENCODE project revealed that Myc is bound to the CR2 promoter. Altogether the data strongly suggest that CR2 is a novel Myc target gene and this may explain the association of Burkitt lymphoma in EBV infection.