Junk DNA: goodbye!: ENCODE third stage (Introduction)

by David Turell , Saturday, August 01, 2020, 14:53 (1576 days ago) @ David Turell

A series of articles in Nature reveal the new regulatory findings:

https://www.nature.com/articles/d41586-020-02139-1

"Less than 2% of the human genome encodes proteins. A grand challenge for genomic sciences has been mapping the functional elements — the regions that determine the extent to which genes are expressed — in the remaining 98% of our DNA. The Encyclopedia of DNA Elements (ENCODE) project, among other large collaborative efforts, was established in 2003 to create a catalogue of these functional elements and to outline their roles in regulating gene expression. In nine papers in Nature5–13, the ENCODE consortium delivers the third phase of its valuable project.

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"Highly occupied target regions have been described before, but — by analysing the patterns in which proteins co-assemble at these regions, and the DNA sequences to which they bind — Partridge et al. have provided the first comprehensive evidence to support a speculative model of HOT-region formation. Under this model, a set of anchor DNA sequences first recruit specific transcription factors. These proteins increase chromatin accessibility, then serve as a core around which other binding proteins aggregate in a manner that is independent of DNA sequence. This could happen through protein–protein interactions and chromatin loops, which might link together multiple distant CREs.

"To further understand how distant CREs work together, Grubert et al.9 mapped chromatin loops in 24 human cell types. They showed that differences in chromatin looping between cell types can affect gene expression, by changing which distant enhancer elements regulate a gene, and which sections of a gene are retained after transcription (a process called alternative splicing). Their most intriguing finding was that housekeeping genes (those involved in day-to-day cell maintenance) often interact with just a few enhancer elements, whereas many enhancers make contact with genes that cause disease if one of two copies is mutated. This implies that a simpler circuitry favours steady and constant expression, whereas more-complex circuitry is needed to safeguard the expression of ‘dosage-sensitive’ genes.

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"This catalogue of RNA elements substantially expands our knowledge of the regulatory components encoded in the human genome. It should enable researchers to predict genetic variants that alter RNA processing, and will constitute an invaluable resource for research into how protein–RNA interactions are regulated.

"The third phase of the ENCODE project is a tour de force. But because many regulatory elements act only in specific cell types or at particular times, it is not possible to precisely assess the completeness of the encyclopedia. It would be interesting to see how the project might incorporate single-cell technologies to tease out spatio-temporal-specific elements and so to further unveil the fundamentals of gene regulation."

Comment: Little junk left. This highly complex review article of over 6,000 papers cannot be reproduced here. CRE's are highly specific regulatory loop areas in DNA. Log in to see the diagrams. Amazingly complex. Our small genome, producing amazingly complex us, had to have these many levels of control and modifications.