Chromatin state segmentation - direction of effect of the identified enhancer

Question

[iphoenix2100]

Dear all,

I am using this UCSC genome browser to do some functional annotation on the top SNP and its high LD SNPs. And would like to know the chromatin state segmentation.

My top SNP is located in the intergenic region of GENE1 and GENE2. From the UCSC chromatin data is seems like both these genes are located in the active promoter regions. While my top SNP locus is located in the Strong enhancer region.

My question is, if my top SNP locus is a strong enhancer how would I know - which gene (GENE1 or GENE2) it has effect on (i.e. Enhance the gene expression)

Is there something like the closest gene to the topSNP has more effect!!?

Thanks
M

Answer 1

[Ryan Dale]

It's difficult to say, because:

• One enhancer can work on many genes
• Many enhancers can work on one gene
• Genomic distance does not always correspond to physical, 3D distance in the nucleus. For example Ghavi-Helm et al 2014's Fig 2 shows a functional enhancer 250kb away (in genomic coords) from the gene it targets.
• Even knowing the 3D distances, just because regions are contacting and look like an enhancer doesn't mean they are acting as a functional enhancer and sometimes can be repressive (e.g., Shoenfelder et al 2015).

You might get some insight from Jager et al 2015 who show the use of Capture Hi-C on risk loci to identify candidate regulatory targets . . . but it doesn't look like they show direct functional data.