ENCODE4 cCREs and ENCODE4 Regulation tracks released for human (hg38) and mouse (mm10)

[Gerardo Perez]

Hello Everyone,

We are excited to announce our major release of the ENCODE4 data collection on the UCSC Genome Browser for both the human (hg38/GRCh38) and mouse (mm10/GRCm38) assemblies. This release consists of two major components: the ENCODE Registry of cCREs (candidate Cis-Regulatory Elements) container, and the new ENCODE4 Regulation container, both described in Moore et al., Nature 2026.

Together, these tracks represent the final ENCODE Phase 4 data release integrated into the browser and cover chromatin accessibility, histone modification and CTCF ChIP-seq, transcription factor binding, and transcription across thousands of individual biosamples. As part of this release, the ENCODE4 cCREs and ENCODE4 Regulation tracks are now the default regulation tracks shown on hg38 and mm10, replacing the previous ENCODE3 cCREs and ENCODE3 Regulation tracks. The ENCODE3 tracks remain available for archival use.

The ENCODE4 Registry of cCREs, Core Collection, and H3K27ac (Layered) Regulation tracks at the HBB locus on hg38.

ENCODE4 cCREs (hg38 and mm10)

The ENCODE Registry of candidate Cis-Regulatory Elements integrates chromatin accessibility and ChIP-seq signals across thousands of biosamples into a biosample-agnostic annotation of the regulatory landscape. Human and mouse are now both up-to-date at ENCODE4:

• ENCODE4 cCREs hg38 and mm10: 2,348,854 human and 926,843 mouse cCREs identified and classified using the ENCODE4 integrative analysis pipeline across ENCODE biosamples. Human cCREs were originally announced in January 2026.
• ENCODE4 Core Collection hg38 and mm10: Biosample-specific cCREs alongside underlying epigenomic signals for the ENCODE4 Core Collection: 170 human and 18 mouse biosamples that were comprehensively profiled with all four core assays (DNase-seq, H3K4me3 ChIP-seq, H3K27ac ChIP-seq, and CTCF ChIP-seq).

Both human and mouse cCREs are colored by their putative functional assignment. See the description page for the full classification scheme.

ENCODE4 Regulation container (hg38 and mm10)

The new ENCODE4 Regulation container for hg38 and mm10 brings the underlying ENCODE4 experimental data directly into the browser. The container combines organ-averaged summary tracks with searchable, faceted views of thousands of individual experiments across both peak and signal data types. The following subtracks are available:

Organ-averaged summary tracks (Layered): transparent overlays of signal averaged across biosamples from the same organ or tissue. Each track uses consistent per-organ colors so the same organ is comparable across assays:

• H3K27ac (Layered) hg38 and mm10: histone modification associated with active enhancers and promoters, shown as the default track.
• DNase (Layered) hg38 and mm10: open chromatin identified by DNase I hypersensitivity.
• ATAC (Layered) hg38 and mm10: open chromatin identified by Tn5 transposase insertion.
• H3K4me3 (Layered) hg38 and mm10: histone modification associated with active and poised promoters.
• CTCF (Layered) hg38 and mm10: CTCF binding, marking insulators and chromatin loop anchors.
• Transcription (Layered) hg38 and mm10: strand-specific total RNA-seq signal, averaged by organ.

Transcription factor peak track hg38: TF rPeaks, representative peak clusters for 912 DNA-associated proteins across 1,152 biosamples, derived from the ENCODE4 TF ChIP-seq collection, with linkouts to SCREEN and FactorBook.

Individual-experiment tracks (Indiv.): searchable, faceted composites providing access to the underlying data behind the summary tracks. Each experiment is shown as a Signal (bigWig) subtrack and, where available, a Peak (bigBed) subtrack:

• DNase/ATAC/Histone/CTCF (Indiv.) hg38: 6,353 subtracks (3,199 signal + 3,154 peak) covering DNase-seq, ATAC-seq, and ChIP-seq for H3K4me3, H3K27ac, and CTCF. Filterable by assay, organ, biosample type, life stage, and data type. mm10 equivalent: 1,178 subtracks.
• TF ChIP-seq (Indiv.) hg38: 4,964 subtracks (2,462 signal + 2,502 peak) for ChIP-seq of individual transcription factors, DNA-associated proteins, RNA polymerase, and chromatin regulators. The experimental basis for the TF rPeaks track above. mm10 equivalent: 334 subtracks.
• RNA-seq (Indiv.) hg38: 1,046 strand-specific total RNA-seq signal subtracks from individual biosamples. mm10 equivalent: 1,054 subtracks.

DNase and H3K27ac (Layered) tracks, plus K562 signal and peak tracks from the DNase/ATAC/Histone/CTCF (Indiv.) faceted composite, at the HBB locus on hg38.

For details, please see the individual track description pages, as well as Moore et al. An Expanded Registry of Candidate cis-Regulatory Elements for Studying Transcriptional Regulation. Nature. 2026 January 7. PMID: 39763870; PMC: PMC11703161.

This dataset was produced by the ENCODE Data Analysis Center (Weng lab at UMass Chan Medical School). Thanks to Mingshi Gao, Jill Moore, and Zhiping Weng for creating and improving the expansive track hubs for ENCODE4 and for iterating with us to bring them to the browser as native tracks. We also thank the ENCODE Consortium, the ENCODE production laboratories, and the ENCODE Data Coordination Center for generating and processing the underlying experiments, and Gerardo Perez, Brian Raney, Max Haeussler, and Lou Nassar for building and reviewing these tracks.