How to identify epigenetic complexes and transcription factors targeting list of genes?

Question

[ivana.ribarski-chorev]

Hello,

I have list of genes from RNA-seq analysis, that I would like to check if they are targeted and by which:

• epigenetic complexes such as MLL, Compass, Polycomb etc.
• transcription factors

Is there a site for entering a list of genes and getting output of which TFs and/or epi-complexes target these genes? It should be bovine or human databases. Or maybe a package in R I can use?

I'm seeking to get per gene - which TF/complex is binding it.

I found TFs sites - but they don't allow entering a list, just one gene each time (I have lists of 1000-2000 genes). In Bioconductor I didn't find any package for this, since they need also Chip data, and I have only RNA-seq data.

(My background: PhD student. Have experience with R. I'm working on bovine cells, but I have transformed the gene names to human orthologs as nearly every databases are human or mouse).

Any advice is appreciated, Ivana

[Papyrus]

A very quick thing you could do, without using information on the gene coordinates or TF binding site coordinates, is to use your gene name list to screen a database of gene sets which defines TFs and the genes that they target. For example, targets for TFs defined by GTRD are nicely compiled by MsigDB (collection C3) and accessible through an R package:

library(msigdbr)
# Load list of TF targets
gtrd <- msigdbr(species = "human", category = "C3", subcategory = "TFT:GTRD")
# You could loop through your gene list to extract the associated TFs. For example, to see for which TFs APOE is a target
gtrd[grepl("APOE",gtrd$gene_symbol),]

[ivana.ribarski-chorev]

Hi, Thank you very much, very helpful for TFs analysis.

If anyone else has advice for the second part - the epigenetic complexes, would be highly appreciated. For example, In one of treatment groups I found downregulated enrichment of all MLLs, COMPASS, SWI and PcG complexes. And would like to have list of their targets (e.g. bivalent genes). OR I have other gene list, which I would like to know their expression (up or down regulated) and methylation status in normal mesenchymal stem cells. (so I can compare to my experiment results).

[Jeremy]

Another way to look for TFs is using g:Profiler (link below). You can input your gene list, click "Run Query", and then select the "Detailed Results" tab. This will show predicted TFs for each gene. It works for human, and cow is available, although I haven't tried it with the latter.

g:Profiler

[ivana.ribarski-chorev]

Thank you.