Genome complexity: gene expression controls (Introduction)

by David Turell , Sunday, May 05, 2019, 02:12 (1819 days ago) @ David Turell

Found to be in independent blocks:

https://www.sciencedaily.com/releases/2019/05/190502143513.htm

"The analysis of the chromatin profiles allowed the scientists to make a first important discovery. "Regulatory activity appears to be organized in fully independent blocks, with series of regulatory elements on the same genomic region being all high or all low at the same time," describes Alexandre Reymond, professor at the Center for Integrative Genomics, UNIL Faculty of Biology and Medicine, who co-lead this work. "As if regulatory elements were stuck together in genomic Lego blocks!" Other geneticists had already pinpointed rather large structures -- called "topologically associating domain" or TAD -- that play a role in gene regulation. However, the "blocks" here identified -- named CRDs -- are of much smaller size, enabling the definition of a much finer resolution map of gene expression.

'To understand their function, the scientists built specific models allowing to measure how genetic variation impacts on these structures, which in turn increase or decrease gene activity. By encompassing several hundreds of samples, the scientists found genetic variants that not only increase or decrease gene expression, but that have the power to change the very structure of these blocks by, for instance, splitting one block into two fully separated structures. By doing so, they change the landscape of regulation, and therefore gene expression.

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"our model shows that regulatory elements could very well be on another chromosome. Because of the nuclear 3-D structure that brings regions together, a cross-talk of regions can take place in any of our 23 chromosomes, with "trans-regulatory hubs" affecting genes anywhere."
The geneticists were able to create statistical models showing what genetic variant influences what block of chromatin that, in turn, affects multiple genes across the genome.

"In addition, if the identification of gene mutations are relatively easy to observe, the same for regulatory elements -- located in the non-coding DNA -- is more problematic. "Indeed, as we do not understand their "grammar" it is difficult to identify if mutations will have an influence, positive or negative. By pooling them together, we were able to design a method to search for rare variants in non-coding regions" explains Olivier Delaneau. "For the first time, we provide a framework of the burden of complex diseases in the non-coding DNA."

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"By incorporating the complexity of the genome into a single model, the scientists provide a tree of correlations of all regulatory elements across the whole genome. "Every node of this tree can then be analysed to summarize the effects of that node as well as the variability of all regulatory elements below that could be relevant to a certain phenotype" indicates Alexandre Reymond. This structure allows reducing the number of hypotheses, and opens up a whole new world in the study of the effect of genetic variation in genome function."

Comment: This article shows an attempt to unravel the 3-D nature of gene controls, which are highly complex, nothing a chance process could ever develop. Pure evidence of design.