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ENCODE mapped long-range looping interactions between functional elements and genes, placing them in a three-dimensional context to reveal their functional relationships
ENCODE provides an initial interpretation of many human variants and plausible leads for the role of many variants identified in genome-wide association studies
First they sequenced it. Now they have surveyed its hinterlands. But no one knows how much more information the human genome holds, or when to stop looking for it.
To be successful, consortia need clear management, codes of conduct and participants who are committed to working for the common good, says ENCODE lead analysis coordinator Ewan Birney.
The Encyclopedia of DNA Elements (ENCODE) project dishes up a hearty banquet of data that illuminate the roles of the functional elements of the human genome. Here, six scientists describe the project and discuss how the data are influencing research directions across many fields. See Articles p.57, p.75, p.83, p.91, p.101 & Letter p.109
This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.
A description is given of the ENCODE effort to provide a complete catalogue of primary and processed RNAs found either in specific subcellular compartments or throughout the cell, revealing that three-quarters of the human genome can be transcribed, and providing a wealth of information on the range and levels of expression, localization, processing fates and modifications of known and previously unannotated RNAs.
An extensive map of human DNase I hypersensitive sites, markers of regulatory DNA, in 125 diverse cell and tissue types is described; integration of this information with other ENCODE-generated data sets identifies new relationships between chromatin accessibility, transcription, DNA methylation and regulatory factor occupancy patterns.
DNase I footprinting in 41 cell and tissue types reveals millions of short sequence elements encoding an expansive repertoire of conserved recognition sequences for DNA-binding proteins.
A description is given of the ENCODE consortium’s efforts to examine the principles of human transcriptional regulatory networks; the results are integrated with other genomic information to form a hierarchical meta-network where different levels have distinct properties.
Chromosome conformation capture carbon copy (5C) is used to look at the relationships between functional elements and distal target genes in 1% of the human genome in three dimensions; the study describes numerous long-range interactions between promoters and distal sites that include elements resembling enhancers, promoters and CTCF-bound sites, their genomic distribution and complex interactions.