Novel long-range regulatory mechanisms controlling <italic>PKD2</italic> gene expression.

Background: <italic>Cis</italic>-regulatory elements control gene expression over large distances through the formation of chromatin loops, which allow contact between enhancers and gene promoters. Alterations in <italic>cis</italic>-acting regulatory systems could be linked to human genetic diseases. Here, we analyse the spatial organization of a large region spanning the polycystic kidney disease 2 (<italic>PKD2</italic>) gene, one of the genes responsible of autosomal dominant polycystic kidney disease (ADPKD). Results: By using chromosome conformation capture carbon copy (5C) technology in primary human renal cyst epithelial cells, we identify novel contacts of the <italic>PKD2</italic> promoter with chromatin regions, which display characteristics of regulatory elements. In parallel, by using functional analysis with a reporter assay, we demonstrate that three DNAse I hypersensitive sites regions are involved in the regulation of <italic>PKD2</italic> gene expression. Conclusions: Finally, through alignment of CCCTC-binding factor (CTCF) sites, we suggest that these novel enhancer elements are brought to the <italic>PKD2</italic> promoter by chromatin looping via the recruitment of CTCF. [ABSTRACT FROM AUTHOR]