828e8fde956c566c299dd09ccde15f217de365a3
lrnassar
  Wed Jan 7 16:54:30 2026 -0800
Final touches to the track, feedback from Zhiping. Reordering the registry tracks to be alphbetical by longLabel, but still keep data types together and updating the refences to the nature article that has now published. Refs #34109

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 <h2>Description</h2>
 <p>
 This track displays the <em>ENCODE Registry of candidate cis-Regulatory Elements</em> (cCREs) 
 in the human genome from ENCODE 4. A total of <b>2,348,854</b> elements identified and classified by the 
 ENCODE Data Analysis Center according to biochemical signatures. Most cCREs are anchored on 
 DNase hypersensitive sites further annotated with histone modifications (H3K4me3 and H3K27ac) 
 or CTCF binding measured by ChIP-seq experiments. In this latest version of the Registry (V4), 
 the representative DNase hypersensitive sites (rDHSs) were supplemented 
 with 86,748 representative transcription factor ChIP-seq peaks (TF 
 rPeaks)—peaks that represent binding sites for at least five TFs. The Registry of cCREs is 
 one of the core components of the integrative level of the ENCODE Encyclopedia of DNA Elements.</p>
 
 <p>Additional exploration of the cCREs and underlying raw ENCODE signal data can be done with the
 <b>Core Collection</b> track. The data is also available on the <a 
 target=" blank" href="https://screen.wenglab.org/">SCREEN</a> (Search Candidate cis-Regulatory 
 Elements) web tool, designed specifically for the Registry, accessible by item mouseovers and linkouts from the 
 track details page.</p>
 
 <h2>Display Conventions and Configurations</h2>
 <p>
 Each cCRE is displayed as a colored box by type, which reflects its putative functional assignment 
 based on biochemical signatures and genomic context:</p>
 <p>
 <img src="../images/encode4cCREs.png" alt="Graphic of cCRE classifications" width="40%"></p>
 <p>
 Mousing over the data will display the accession ID, the assigned cCRE class type, and the Max-Z scores
 for the various underlying biosignals (DNase, H3K4me3, H3K27ac, CTCF). A track filter is also available
 to selectively show items based on their cCRE class type.</p>
 
 <h2>Methods</h2>
 <p>
 Candidate cis-regulatory elements (cCREs) were first anchored on nucleosome-sized DNase 
 hypersensitive sites (rDHSs) identified from DNase-seq data. These rDHSs were then annotated 
 using ChIP-seq data for histone modifications—H3K4me3 and H3K27ac, marking promoters and 
 enhancers, respectively—and CTCF, marking insulators. To supplement rDHS-anchored cCRE 
 definitions, transcription factor ChIP-seq peaks were incorporated, enabling identification 
 of cCREs even in regions of low chromatin accessibility. Although not used for anchoring, 
 ATAC-seq data were used to assess chromatin accessibility in biosamples lacking DNase-seq.</p>
 
 <p>
 Classification of cCRE's was performed based on the following criteria:</p>
 <ol>
 <li><strong><span style="color: #ff0000;">Promoter-like signatures (promoter)</span></strong> 
 must fall within 200 bp of a TSS and have high chromatin accessibility and H3K4me3 signals.</li>
 <li><strong><span style="color: #ffa700;">TSS-proximal enhancer-like signatures (proximal 
 enhancer)</span></strong> have high chromatin accessibility and H3K27ac signals and are 
 within 2 kb of an annotated TSS. If they are within 200 bp of a TSS, they must 
 also have low H3K4me3 signal.</li>
 <li><strong><span style="color: #ffcd00;">TSS-distal enhancer-like signatures 
 (distal enhancer)</span></strong> have high chromatin accessibility and H3K27ac signals 
 and are farther than 2 kb from an annotated TSS.</li>
 <li><strong><span style="color: #ffaaaa;">Chromatin accessibility + 
 H3K4me3 (CA-H3K4me3)</strong></span> have high chromatin accessibility and H3K4me3 
 signals but low H3K27ac signals and do not fall within 200 bp of a TSS.</li>
 <li><strong><span style="color: #00b0f0;">Chromatin accessibility + 
 CTCF (CA-CTCF)</strong></span>have high chromatin accessibility and CTCF signals 
 but low H3K4me3 and H3K27ac signals.</li>
 <li><strong><span style="color: #be28e5;">Chromatin accessibility + 
 transcription factor (CA-TF)</strong></span> have high chromatin accessibility, 
 low H3K4me3, H3K27ac, and CTCF signals, and are bound by a transcription factor.</li>
 <li><strong><span style="color: #06da93;">Chromatin accessibility 
 (CA)</strong></span>have high chromatin accessibility and low H3K4me3, H3K27ac, and 
 CTCF signals.</li>
 <li><strong><span style="color: #d876ec;">Transcription factor 
 (TF)</strong></span> have low chromatin accessibility, low H3K4me3, H3K27ac, 
 and CTCF signals and are bound by a transcription factor.</li>
 </ol>
 
 <h2>Data Access</h2>
 <p>
 The ENCODE accession numbers of the constituent datasets at the <a target="_blank"
 href="https://encodeproject.org/">ENCODE Portal</a> are available from the cCRE details page.</p>
 <p>
 The data in this track can be interactively explored with the <a target="_blank" 
 href="/cgi-bin/hgTables">Table Browser</a> or the <a target="_blank" 
 href="/cgi-bin/hgIntegrator">Data Integrator</a>. The data can be accessed from 
 scripts through our a <target="_blank" href="https://api.genome.ucsc.edu/">API</a>, 
 the track name is "cCREregistry".</p>
 <p>
 For automated download and analysis, this annotation is stored in a bigBed file 
 that can be downloaded from <a target="_blank" 
 href="http://hgdownload.soe.ucsc.edu/gbdb/hg38/encode4/ccre/">our download server</a>. 
 The file for this track is called cCREregistry.bb. Individual regions or the whole genome 
 annotation can be obtained using our tool bigBedToBed which can be compiled from the source 
 code or downloaded as a precompiled binary for your system. Instructions for downloading 
 source code and binaries can be found <a target="_blank" 
 href="http://hgdownload.soe.ucsc.edu/downloads.html#utilities downloads">here</a>. 
 The tool can also be used to obtain only features within a given range, e.g.<br><br>
 <code>bigBedToBed http://hgdownload.soe.ucsc.edu/gbdb/hg38/encode4/ccre/cCREregistry.bb -chrom=chr21 -start=0 -end=100000000 stdout</code></p>
 
 <h2>Credits</h2>
 <p>
 Data were generated by the ENCODE Consortium. The data were further processed for 
 visualization through a collaborative effort between the <a target="_blank" 
 href="https://www.umassmed.edu/zlab">Weng lab</a> and the <a target="_blank" 
 href="https://sites.google.com/view/moore-lab/">Moore lab</a> at UMass Chan Medical 
 School (funded by NIH grant HG012343). Integration and visualization were developed 
 by Drs. Mingshi Gao, Jill Moore, and Zhiping Weng at UMass Chan Medical School, who were 
 part of the ENCODE Data Analysis Center. We thank the ENCODE production labs 
 for generating the data.</p>
 
 <h2>References</h2>
 <p>
 ENCODE Project Consortium, Moore JE, Purcaro MJ, Pratt HE, Epstein CB, Shoresh N, Adrian J, Kawli T,
 Davis CA, Dobin A <em>et al</em>.
 <a href="https://doi.org/10.1038/s41586-020-2493-4" target="_blank">
 Expanded encyclopaedias of DNA elements in the human and mouse genomes</a>.
 <em>Nature</em>. 2020 Jul;583(7818):699-710.
 PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/32728249" target="_blank">32728249</a>; PMC: <a
 href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410828/" target="_blank">PMC7410828</a>
 </p>
 <p>
 Moore JE, Pratt HE, Fan K, Phalke N, Fisher J, Elhajjajy SI, Andrews G, Gao M, Shedd N, Fu Y <em>et
 al</em>.
-<a href="https://doi.org/10.1101/2024.12.26.629296" target="_blank">
+<a href="https://www.nature.com/articles/s41586-025-09909-9" target="_blank">
 An Expanded Registry of Candidate cis-Regulatory Elements for Studying Transcriptional
 Regulation</a>.
-<em>bioRxiv</em>. 2024 Dec 26;.
+<em>Nature</em>. 2026 January 7.
 PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/39763870" target="_blank">39763870</a>; PMC: <a
 href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703161/" target="_blank">PMC11703161</a>
 </p>