A methyl-sensitive element induces bidirectional transcription in TATA-less CpG island-associated promoters

How TATA-less promoters such as those within CpG islands (CGI) control gene expression is still a subject of active research. Here, we have identified the “CGCG element”, a ten-base pair motif with a consensus sequence of TCTCGCGAGA present in a group of promoter-associated CGI-enriched in ribosomal protein and housekeeping genes. This element is evolutionarily conserved in vertebrates, found in DNase-accessible regions and employs RNA Pol II to activate gene expression. Through analysis of capped-nascent transcripts and supporting evidence from reporter assays, we demonstrate that this element activates bidirectional transcription through divergent start sites. Methylation of this element abrogates the associated promoter activity. When coincident with a TATA-box, directional transcription remains CGCG-dependent. Because the CGCG element is sufficient to drive transcription, we propose that its unmethylated form functions as a heretofore undescribed promoter element of a group of TATA-less CGI-associated promoters.