Human PRE-PIK3C2B exhibits long-range intra- and inter-chromosomal interactions with genomic regions enriched in repressive marks.

Abstract

Human PRE-PIK3C2B is a dual nature polycomb response element that interacts with both polycomb as well as trithorax members. In the current study, using 4C-Seq (Capturing Circular Chromosomal Conformation-Sequencing), we identified long-range chromatin interactions associated with PRE-PIK3C2B and validated them with 3C-PCR. We identified both intra-as well as inter-chromosomal interactions, a large proportion of which were found to be closely distributed around transcriptional start sites (TSS). A significant number of interactions were also found to be associated with heterochromatic regions. Meta-analysis of ENCODE ChIP-Seq data identified an overall enrichment of YY1, CTCF as well as histone modification such as H3K4me3 and H3K27me marks in different cell lines. Almost 90% interactions were derived from either intronic or intergenic regions. among which large proportions of intronic interactors were either unique sequences or LINE/SINE derived. In case of intergenic interactions, majority of the interaction were associated with LINE/SINE repeats. We further found that genes proximal to the interactor sequences were co-expressed, they showed reduced expression. To the best of our knowledge this is one of the early demonstrations of long-range interaction of PRE sequences in human genome.