fa272dac584b8d450211f426b50c5e9e6de114c8 mspeir Tue Sep 22 08:40:34 2026 -0700 New FAQ page on regulation and cis-regulatory tracks, refs #24610 Adds FAQ/FAQregulation.html, the page requested in this ticket since 2019: where to find transcription factor binding site data, and how the various cis-regulatory tracks relate to each other. The page is organized around the measured vs predicted distinction, which is what most of the mailing list questions turn on, and then covers which TFBS tracks to use, what to do when a factor is in none of them, loading ENCODE portal data through the portal's own Visualize button, promoters, enhancers, cCREs, restricting to a cell type, and working outward from a gene. It ends with a summary table of 16 tracks. Assembly coverage is given per track and every assembly name is a link to that track's description page on that assembly, since coverage varies a lot (mm39 carries only three of these tracks, and TFBS Conserved was never built for hg38). Also adds the category to FAQ/index.html and a cross-link from the promoter sequence question in FAQ/FAQdownloads.html. Co-Authored-By: Claude Opus 5 (1M context) diff --git src/hg/htdocs/FAQ/FAQregulation.html src/hg/htdocs/FAQ/FAQregulation.html new file mode 100755 index 00000000000..575f02c1a79 --- /dev/null +++ src/hg/htdocs/FAQ/FAQregulation.html @@ -0,0 +1,521 @@ + + + + + + + +

Frequently Asked Questions: Regulation and cis-regulatory tracks

+ +

Topics

+ + +
+

+Return to FAQ Table of Contents

+ +

+The assembly names after each track are links. They open that track's description page on +that assembly, which gives the methods, the data version and the citation. Coverage varies a +lot between assemblies, so check the list before you assume a track exists on the genome you +work with.

+ + +

The basics

+

+The Genome Browser carries a large number of tracks that annotate regulatory regions. Most of +them are in the Regulation track group, which you will find below the browser image on +the main browser page. It is not always obvious which +one you want, because these tracks answer quite different questions even when they all look +like boxes on the screen.

+ +
What is the difference between measured and predicted binding sites?
+

+Nearly every question we get about these tracks comes down to this distinction.

+

+A measured binding site comes from an experiment, usually ChIP-seq, in which one +protein was pulled down in one cell type under one set of conditions. The site is real in the +sense that the factor was found there in that experiment. It tells you nothing about other cell +types, and the experiment has to have been done for your factor and your tissue for the data to +exist at all.

+

+A predicted binding site comes from scanning the genome sequence for a motif, a short +pattern that the factor is known to prefer. Predictions exist everywhere in the genome for every +factor with a known motif, regardless of cell type, and most of them are not bound in +vivo. A typical transcription factor motif occurs hundreds of thousands of times in the +human genome, while the factor binds only a few thousand of those positions in any given cell.

+

+Neither kind is better than the other. To find out where a factor was actually found, use a +measured track. To find out whether some sequence you care about, a variant or a promoter +fragment, could plausibly be bound, use a predicted track. What you cannot do is cite a +prediction as evidence that the factor binds there.

+ + +

Transcription factor binding sites

+ +
Which tracks show transcription factor binding sites?
+

+For human, three tracks cover most needs. All three are in the Regulation group.

+ +

+Two older tracks still come up in questions. TFBS Conserved shows predicted +sites that are conserved across human, mouse and rat, on +hg17, +hg18 and +hg19 only; it has not been updated in +many years and +there is no hg38 version. ORegAnno is a curated collection of regulatory +elements taken from the literature, so it is small but every entry has a citation, on +hg19, +hg38, +mm10 and +dm6.

+ + +
I cannot find my transcription factor in any track. Where else can I look?
+

+First check whether the experiment simply has not been done. ReMap covers the published ChIP-seq +experiments that were available when it was built, so if your factor is absent from ReMap there +may be no public ChIP-seq for it in that organism. The +ReMap website lets you search by target +and download the peaks per factor, and that is the quickest way to check.

+

+If the experiment exists but is newer than our tracks, or was done in a cell type we do not +carry, you will need to bring the data in yourself. The usual sources are:

+ + + +
How do I display ENCODE data that is not already a track?
+

+You do not need to download anything or write a custom track by hand. The ENCODE portal will +open its data in the Genome Browser for you.

+
    +
  1. + Search the ENCODE portal for what you want, narrowing the results with the filters + down the left side. Assay title, Target of assay (the + factor), Biosample (the cell type or tissue) and Genome + assembly are the useful ones.
    2. +
  2. + Click the Visualize button above the result list.
    3. +
  3. + Pick your assembly in the panel that opens, then click UCSC.
    4. +
+

+The Browser opens with every experiment in your filtered result set loaded as a track hub, so +this works just as well for one experiment as for fifty. Restrict the search before you +visualize, since a broad filter can attach a very large number of tracks at once.

+

+ENCODE also publishes a hub for each individual experiment, which is handy if you are scripting +or want to keep a link in a session. Substitute the accession into this URL:

+
https://www.encodeproject.org/experiments/ENCSR000AKO/@@hub/hub.txt
+

+and load it from the My Hubs tab of the Track +Hubs page, or by appending it to a browser URL as +hgTracks?db=hg38&hubUrl= followed by the hub address.

+

+If you would rather place a single file yourself, note that ENCODE distributes peaks as bigBed +and signal as bigWig, both of which the Browser reads directly. Copy the file URL from the portal; +you do not +need to download the file. Then paste one custom track line at +Add Custom Tracks:

+
track type=bigBed name="CTCF K562 peaks" bigDataUrl=https://www.encodeproject.org/files/ENCFF002CEL/@@download/ENCFF002CEL.bigBed
+

+The Browser does not download the whole file. bigBed and bigWig are indexed, so it fetches only +the part covering the region you are looking at, which is why a multi-gigabyte signal file opens +in a moment. Full instructions are on the +custom tracks help page and the +track hub help page.

+ + +

Promoters, enhancers and other elements

+ +
Which tracks show promoters?
+

+It depends on what you mean by a promoter, and the tracks disagree enough that it matters.

+ + + +
Which tracks show enhancers and other regulatory elements?
+ +

+For the chromatin evidence behind the called elements, see +ENCODE4 Regulation on hg38, which +carries DNase, ATAC-seq, histone +modification and CTCF signal organized by tissue, and the older ENCODE3 Regulation container on +hg19 and +hg38.

+ + +
What are cCREs, and which cCRE track should I use?
+

+A candidate cis-regulatory element, or cCRE, is a region that looks regulatory in chromatin +data. Nobody has shown that it regulates anything. ENCODE built the +Registry of cCREs by combining DNase accessibility with histone modification and CTCF signal +across many biosamples, then classifying each region as promoter-like, enhancer-like, CTCF-only +and so on. The word candidate is doing real work here: these are regions worth testing, +not confirmed regulatory elements.

+

+The ENCODE cCREs container on hg38 holds +several versions. The ENCODE4 +cCREs registry is the current one and should be your default. The ENCODE4 Core +Collection is a smaller, higher-confidence subset. ENCODE3 cCREs is the +earlier release, kept because a great many published analyses used it and coordinates need to +stay reproducible. The container also carries per-biosample subtracks, which is how you restrict +the classification to one cell type. Mouse +mm10 carries the same three versions.

+ + +

Working with the data

+ +
How do I restrict a search to one cell type or tissue?
+

+Most of the large regulatory tracks are composites or superTracks holding many subtracks, one +per cell type or experiment, and they arrive with only a summary view turned on. Click the track +name to open its configuration page, where you will find the list of subtracks and, on the +bigger tracks, filters. ReMap, for instance, lets you filter by transcription factor directly in +the track settings, so you can show one factor across all its experiments.

+

+To find a track rather than configure one, the +Track Search page searches track +names and descriptions across the whole assembly, which is usually faster than reading through +the track groups.

+ + +
I have a gene. How do I find the factors that regulate it?
+

+No single track answers this, so you have to work outward from the gene.

+
    +
  1. + Navigate to the gene and zoom out far enough to include the surrounding non-coding sequence. + Regulatory elements are often tens or hundreds of kilobases away, and the nearest gene to an + element is frequently not its target.
    2. +
  2. + Turn on GeneHancer. Its interaction arcs will show which elements have been linked to your + gene, including distant ones, which narrows the search from the whole neighborhood to a + handful of regions.
    3. +
  3. + Turn on ReMap or TF ChIP and look at which factors have peaks in those regions. This gives you + factors that were measured at that position in some cell type.
    4. +
  4. + Check whether any of those cell types are relevant to your biology. A peak in K562 says little + about neurons.
    5. +
  5. + If you need candidates in a cell type nobody has assayed, fall back to JASPAR predictions + within the GeneHancer elements, and treat the result as hypotheses to test.
    6. +
+

+To do this systematically, the +Data Integrator will intersect two or more tracks and +return a table, and the Table Browser will do the same for a +region or for a list of genes.

+ + +
What is available for assemblies other than human and mouse?
+

+Considerably less, and this is a matter of what data exists rather than what we have loaded. The +large regulatory resources were built for human first and mouse second. JASPAR predictions are +the most widely available, since they only require the genome sequence and a motif, and are +present for zebrafish, fly, worm, chicken, sea squirt and yeast in addition to human and mouse. +ReMap and ORegAnno cover fly. Most of the remaining tracks described on this page are human and +mouse only.

+

+Coverage also differs between assemblies of the same organism. On mouse, mm10 carries most of +the regulatory tracks while mm39 has only JASPAR, ReMap and VISTA, because several of the source +projects have not released mm39 versions. If a track you need is on mm10 but not mm39, the +LiftOver tool can convert coordinates between the two, +though you should check the result. Human has the same problem on a smaller scale: a few of +these tracks are still hg19 only, and TFBS Conserved was never rebuilt for hg38.

+

+For assemblies not hosted at UCSC, or for tracks we do not carry, check the +public hubs list, where other groups publish data through +our browser.

+ + +

Summary: regulatory tracks by category

+

+Each assembly name below links to that track's description page on that assembly. A few tracks +appear on additional genomes not listed here; use +Track Search to check a genome that is +not shown.

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
TrackWhat it isMeasured or predictedAssemblies
Transcription factor binding
ReMap ChIP-seqPublic ChIP-seq for transcriptional regulators, integratedMeasuredhg19, + hg38, + mm10, + mm39, + dm6
TF ChIP (ENCODE 3 TFBS on hg19)ENCODE 3 TF ChIP-seq peaks, around 340 factors in about 130 cell typesMeasuredhg19, + hg38
JASPAR Transcription FactorsMotif matches from the JASPAR CORE collectionPredictedhg19, + hg38, + mm10, + mm39, + danRer11, + dm6, + ce11, + galGal6, + ci3, + sacCer3
TFBS ConservedConserved motif matches; not updated recently, no hg38 versionPredictedhg17, + hg18, + hg19
ORegAnnoRegulatory elements curated from the literatureMeasured, curatedhg19, + hg38, + mm10, + dm6
Promoters and transcription start sites
EPDnew PromotersExperimentally defined promoters with mapped start sitesMeasuredhg19, + hg38, + mm10
FANTOM5CAGE transcription start sites and their usage per tissueMeasuredhg19, + hg38, + mm10
Enhancers and candidate elements
GeneHancerRegulatory elements linked to predicted target genesMixed, with predicted targetshg19, + hg38
VISTA EnhancersElements tested individually in transgenic mouse assaysMeasured, validatedhg19, + hg38, + mm10, + mm39
ENCODE cCREsCandidate elements classified from chromatin signalPredicted from measured signalhg38, + mm10
RefSeq Functional ElementsNCBI curated non-coding functional elementsMeasured, curatedhg38, + mm10
MPRAsMassively parallel reporter assay activityMeasuredhg38
Chromatin and expression context
ENCODE4 RegulationDNase, ATAC, histone marks and CTCF by tissueMeasuredhg38
ENCODE3 RegulationDNase, histone marks and transcription signalMeasuredhg19, + hg38
Single-cell ATAC-seqAccessibility peaks and signal from Cell Browser datasetsMeasuredhg38, + mm10
GTEx GeneGene expression across 53 tissuesMeasuredhg19, + hg38
GTEx cis-eQTLsVariants associated with expression of nearby genesMeasuredhg38
+ +

+For the full set of tracks on any assembly, open the Regulation group on the +browser page, or use +Track Search.

+ +