Genomics research consortium · BEGINNER LESSON
ENCODE
ENCODE, short for Encyclopedia of DNA Elements, is a public research project that maps candidate functional parts of the human and mouse genomes. It measures biochemical signals linked to genes, gene regulation, and RNA products, then organizes those data into shared annotations.
What ENCODE is
ENCODE is a public research consortium and database effort. Its goal is to identify functional elements in the human and mouse genomes and to share the resulting data freely with the scientific community. In this context, a functional element is a DNA region or RNA product associated with a biological role such as gene control or transcript structure. ENCODE began in 2003 and later expanded through several phases.
[1] Perspectives on ENCODE - PMC - NIH [2] The Encyclopedia of DNA Elements (ENCODE) [3] Introduction to ENCODE Data: Overview of ENCODE Data Types
What it measures
ENCODE measures experimental signs of genome activity rather than only DNA sequence. These signs include transcribed regions, open chromatin, transcription factor binding, histone marks, RNA binding, and 3D chromatin organization. Open chromatin means DNA that is more accessible to cellular proteins. Histone marks are chemical changes on histone proteins around which DNA is wrapped. Transcription factors are proteins that bind DNA to help control gene expression, meaning when a gene is used to make RNA.
[1] Perspectives on ENCODE - PMC - NIH [3] Introduction to ENCODE Data: Overview of ENCODE Data Types
How it works
The project uses many assays, including microarray-based assays, chromatin interaction methods such as ChIA-PET and Hi-C chromosome conformation capture, and newer reporter-based and CRISPR-based genome or epigenome editing methods. These experiments generate biochemical signatures that are then integrated into a registry of candidate cis-regulatory elements, often called cCREs. Cis-regulatory elements are DNA regions that help regulate nearby genes. ENCODE also builds two layers of annotation: direct experimental, or ground-level, data and integrated encyclopedia-level summaries.
[1] Perspectives on ENCODE - PMC - NIH [2] The Encyclopedia of DNA Elements (ENCODE)
What it has found
ENCODE has produced large catalogs of candidate regulatory elements in human and mouse, including about 0.9 million cCREs in human and 0.3 million in mouse in one integrated version. It also showed that genome control is spread across many DNA regions involved in transcription, chromatin organization, and splicing. Splicing is the process that joins pieces of RNA to form a mature transcript. The project has also expanded to include different organisms and broader sample types.
[1] Perspectives on ENCODE - PMC - NIH [2] The Encyclopedia of DNA Elements (ENCODE)
Limitations
ENCODE is powerful for mapping candidate elements, but a map is not the same as a complete functional explanation. Many elements are still not fully annotated, especially those active only in specific cell types, developmental states, or tissues. The texts also note limited knowledge of which transcription factors bind many open chromatin regions, and that full-length transcript structures are known for only a small number of cell types. So ENCODE provides strong evidence for candidates, but many functions still need direct testing.
[1] Perspectives on ENCODE - PMC - NIH [2] The Encyclopedia of DNA Elements (ENCODE) [3] Introduction to ENCODE Data: Overview of ENCODE Data Types
SEE THE IDEA
How ENCODE builds genome annotations
Human or mouse cells or tissues provide DNA, RNA, and chromatin signals.
Methods measure transcribed regions, open chromatin, binding sites, RNA interactions, and 3D DNA contacts.
Signals are grouped into cCREs and other annotations that may regulate genes.
Results are organized into shared databases for researchers to use.
Samples are measured by assays, assays produce signals, signals become candidate annotations, and annotations are shared publicly.
ENCODE turns many kinds of genome-activity measurements into a public catalog of candidate functional elements.
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Sources and further reading
This general lesson was generated from public source material. It explains a concept; it does not interpret a private paper or provide medical advice.