Junk DNA: goodbye!: ENCODE now hedging on 80% (Introduction)

by David Turell , Wednesday, October 12, 2016, 18:53 (2750 days ago) @ David Turell

A guess is more like 20% but more and more modifying areas for gene expression are found in 'dark' or junk DNA as newer techniques tease apart DNA:

http://www.nature.com/nature/journal/v538/n7624/full/538275a.html?WT.ec_id=NATURE-20161...

"Fifteen years ago, scientists celebrated the first draft of the sequenced human genome. At the time, they predicted that humans had between 25,000 and 40,000 genes that code for proteins. That estimate has continued to fall. Humans actually seem to have as few as 19,000 such genes1 — a mere 1–2% of the genome. The key to our complexity lies in how these genes are regulated by the remaining 99% of our DNA, known as the genome's 'dark matter'.

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"So far, the data suggest that there are hundreds of thousands of functional regions in the human genome whose task is to control gene expression: it turns out that much more space in the human genome is devoted to regulating genes than to the genes themselves. Scientists are now trying to validate each predicted element experimentally to ascertain its function — a mammoth task, but one for which they now have a powerful new tool.

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"How much of DNA's dark matter has a function in gene control is still up for debate. In 2012, ENCODE scientists proposed on the basis of biochemical-assay predictions that 80% of the non-coding genome has a function2. But this figure soon proved to be an overestimate as researchers narrowed the definition of 'function' and devised experimental methods, such as reporter assays, to test these functions. “The number still isn't fully known”, in part because the mapping isn't complete, says Michael Snyder, a geneticist at Stanford University in California and a member of ENCODE. “Most people would say between 10% and 20% of the [non-coding] genome is likely to have a function where, if you disrupt it, you will affect something.”

"But regulatory elements have a bewildering array of functions and forms, which makes tackling them a formidable challenge. Even the best-known types, such as spots in the genome known as promoters, which lie next to a gene where transcription begins, and enhancers — regions that when bound by specific transcription factors alter the likelihood of a gene being read — are hard to study. In addition to the sheer number of these sites, estimated at 15 million, enhancers may be positioned thousands of base pairs away from the gene that they control. This makes it tough to predict where their target genes are located and what they do.

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"...the researchers also discovered mysterious sections that they dubbed 'unmarked regulatory elements', or UREs, that do not fit into any category of functional elements. The team is currently exploring how widespread these UREs might be in the genome. This new type of assay, along with other gene-editing-based screens, will play an increasingly important part in the validation of ENCODE candidates, says Sherwood.

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"It's possible that there are still elements in the genome that existing assays have missed. After all, regulatory signals still crop up unexpectedly, such as the UREs in Sherwood's screen. And a team of scientists led by Harvard Medical School immunologist Daniel Tenen discovered10 a potential new class of regulators that seem to control whether a gene is turned on or off by blocking the enzyme DNA methyltransferase 1, which adds methyl groups to silence genes. These elements are dubbed 'extracoding RNAs', and because they can influence silencing in a gene-specific way, have therapeutic potential. Earlier this year, neuroscientist Jeremy Day of the University of Alabama at Birmingham and his colleagues showed in rat neurons that an extracoding RNA influences the transcription of a gene important for memory formation.

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" A spatial understanding of how DNA is packaged into a cell, and of the 3D folding that positions genes in close contact with their regulatory elements, will be key to predicting an element's target genes. The NIH Common Fund has begun the '4D Nucleome' project, for instance, which aims to predict the target genes for every regulatory element. That knowledge will help to fill in the picture of how a given regulatory element influences health and disease."

Comment: Still no idea of how much DNA is useful, as the article explains. Not 80% but how much? Note the idea of 3,4-D relationships I've noted before. With a huge regulatory system, chance invention of human DNA is not possible.