Life Sciences Research for Lifelong Health

Promoter Capture Hi-C

Hi-C libraries are incredibly complex and cannot really identify chromatin interactions between distant genomic sequences at the restriction fragment level with statistical significance unless tens of billions or read-pairs are produced. To get around this shortcoming and to identify distal sequences that significantly interact with gene promoters using a statistical threshold we developed Promoter Capture Hi-C. This involves sequence capture using thousands of biotinylated RNA oligomers complementary to all annotated promoters to specifically enrich for promoter-containing fragments from Hi-C libraries. The enriched promoter-containing fragment libraries are then sequenced with high-throughput paired-end sequencing to reveal long-range, promoter-interacting genomic regions such as enhancers and other potential distal regulatory elements, as well as non-random, promoter-to-promoter contacts in the 3D nuclear space. We have used this data to create a greater understanding of global gene expression control, to assign distal regulatory elements to their target genes, to link human disease-associated variants to their target genes and to assess genome-wide contacts between promoters, which play roles in control of gene transcription and gene repression.

                                                                                                                        Image from Mifsud et al., 2015

For more information see:

The pluripotent regulatory circuitry connecting promoters to their long-range interacting elements
Schoenfelder, et al., (2015) Genome research 25 (4), 582-597.

Mapping long-range promoter contacts in human cells with high-resolution capture Hi-C
Mifsud et al., (2015) Nature genetics 47, 598-606.

Polycomb repressive complex PRC1 spatially constrains the mouse embryonic stem cell genome
Schoenfelder et al., (2015) Nature genetics 47, 1179-1186.