HiC: method of identifying regulatory interactions between genomic loci
The disclosed Hi-C protocol can identify genomic loci that are spatially co-located in vivo. These spatial co-locations may include, but are not limited to, intrachromosomal interactions and/or interchromosomal interactions. Hi-C techniques may be applied to many different scales of interest. For example, on a large scale, Hi-C techniques can be used to identify long-range interactions between distant genomic loci.
1. A method, comprising;
a) providing;
i) a crosslinked mammalian genome comprising a plurality of joins, wherein the each of said plurality of joins comprises two ligated nucleic acid sequences; and
ii) a plurality of paired end sequencing adaptors;
b) ligating said plurality of paired end sequencing adaptors to the said plurality of joins;
c) sequencing each of said two ligated nucleic acid sequences with said plurality of paired end sequencing adaptors; and
d) aligning each of said sequenced two ligated nucleic acid sequences to have identity with a first genomic region and a second genomic region on a mammalian genome reference sequence;
e) detecting a regulatory element within said second genomic region that interacts with said first genomic region.
2. The method of claim 1 , wherein said crosslinked mammalian genome comprises a crosslinked human genome.
3. The method of claim 1 , wherein said crosslinked mammalian genome comprises a crosslinked non-human genome.
4. The method of claim 1 , wherein said first genomic region comprises an open reading frame sequence.
5. The method of claim 1 , wherein said second genomic region comprises a regulatory gene.
6. The method of claim 5 , wherein said regulatory gene interacts with said open reading frame sequence.
7. The method of claim 4 , wherein said open reading frame sequence encodes a protein associated with a medical condition.
8. The method of claim 7 , wherein said medical condition comprises cancer.
9. The method of claim 7 , wherein said medical condition comprises a cardiovascular disease.
10. The method of claim 7 , wherein said medical condition comprises a kidney disease.
11. The method of claim 7 , wherein said medical condition comprises an autoimmune disease.
12. The method of claim 7 , wherein said medical condition comprises a pulmonary disease.
13. The method of claim 7 , wherein said medical condition comprises a pancreatic disease.
14. The method of claim 7 , wherein said medical condition comprises a muscular disease.
15. The method of claim 7 , wherein said medical condition comprises a bone disease.
16. The method of claim 7 , wherein said medical condition comprises a blood disorder.
17. The method of claim 7 , wherein said medical condition comprises a sleep disorder.
18. The method of claim 5 , wherein said regulatory gene comprises an enhancer.
19. The method of claim 5 , wherein said regulatory gene comprises a silencer.
20. The method of claim 5 , wherein said regulatory gene comprises an insulator.