The Encyclopedia of DNA Elements (ENCODE) reveals a human genome more rich and complex than envisioned a decade ago. The work of many biologists shows it is not just the gene, but the network that makes the human genome dynamic.
What’s been found is a regulatory network that has properties similar to the connections in a social network. Using sophisticated mathematical modeling, one team traced the cascade of a half million molecular interactions triggered by 119 transcription factors – proteins that can simultaneously activate or silence thousands of genes. The model shows that these transcription factors interact in a hierarchical fashion, with some factors operating like top-level executives, and some as middle managers or shop foremen. Together they regulate the 20,000 or so genes in the human genome.
By necessity, this hierarchical structure creates information-flow bottlenecks at the level of “middle managers”, which work together to more efficiently regulate target genes and ease the bottlenecks. So the human genome is organized much more democratically than a top-down command system. However, “executive-level” transcription factors do tend to have the most influence in important functions such as driving gene expression, and also have better connections with other genes in different molecular networks. Attesting to their importance to survival, these “executives” tend to be more conserved across populations.
Both the size and flexibility of the human genome makes it different from genomes of many other organisms studied so far. Model organisms such as worms or flies have a simpler diagram — for example, a switch-like promoter close to a gene that is responsible for all its regulation. But the ENCODE project shows dramatically that there are hundreds of thousands of more distant elements – enhancers – that can influence human gene action from afar. Networks regulated by enhancers tend to be wired differently than those regulated by nearby promoters.
• ENCODE: The human encyclopaedia
• Human Genome Is Much More Than Just Genes
• Getting to Know the Genome
• New DNA Encyclopedia Attempts to Map Function of Entire Human Genome
• Cataloging the controlled chaos of the human genome
• Team releases sequel to the human genome
• Major advances in understanding the regulation and organization of the human genome
• Researchers identify biochemical functions for most of the human genome
• DNA database unlocks map to genetic disease
• Decade-long DNA project prompts ‘gene’ redefinition
• Global project reveals just how active our ‘junk’ DNA is
• ENCODE: the rough guide to the human genome
• ENCODE: My own thoughts
• Human genome far more active than thought
• Fighting about ENCODE and junk