RCMC: A Game Changer for Genome-Wide Mapping

Category Science

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MIT researchers have developed a highly detailed 3D genome mapping technique named RCMC that allows much cheaper and more accurate gene and regulatory region analysis. RCMC can be applied to genome areas connected to multiple metabolic disorders and blood conditions to gain insight into gene regulation at an unprecedented resolution.

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Region Capture Micro-C (RCMC), a new technique created by MIT researchers to map the 3D organization of the human genome, provides unparalleled resolution at a far cheaper cost. The MIT researchers used Micro-C, which fragments the genome using the enzyme micrococcal nuclease, to acquire the high resolution required to map particular connections between genes and regulatory regions.

The number of potential genomic locations is reduced by a factor of 1,000 by concentrating on regions of the genome that contain genes of interest, and the cost of sequencing is reduced by a factor of 100,000, or around $1,000. In a recent study, the scientists employed RCMC to investigate five locations with sizes ranging from a few hundred thousand to nearly 2 million base pairs.

RCMC reduces the cost of obtaining high resolution 3D genome maps by a factor of 10,000

They discovered numerous enhancers that interact with Sox2 as well as previously unknown relationships between neighboring genes and enhancers after collecting and sequencing the DNA regions of interest. The method used by the researchers, however, conceals neither the timing nor simultaneity of any of these interactions – nor does it indicate which contact is most crucial.

The MIT team intends to collaborate with scientists at Harvard Medical School to investigate variants linked to metabolic disorders and with scientists at Boston Children's Hospital to apply this type of analysis to genomic regions that have been connected with blood disorders in genome-wide association studies.

RCMC captures the chromatin looping architecture of the entire genome

RCMC offers unprecedented resolution at a much lower cost -- For a quarter of the price of other published techniques, RCMC produces maps that are 100 times more information-rich by concentrating on regions spanning a few million base pairs. Prior to this, obtaining high resolution would have cost millions, if not billions, of dollars. With RCMC, this approach is more reasonably priced at around $1,000.

Combining RCMC with other sequencing methods can provide accurate representations of gene networks and regulatory elements

New tool to study genomic regions linked to blood disorders and metabolic disorders -- In order to apply RCMC to genomic areas connected with blood diseases in genome-wide association studies, the MIT team intends to collaborate with scientists at Boston Children's Hospital. Additionally, they are working with Harvard Medical School experts to investigate variations related to metabolic illnesses. With the help of the new method, it will be possible to analyze the ultrafine chromatin looping architecture and gain new knowledge about the connections between regulatory elements and gene regulation.

With RCMC, the MIT team was able to detect novel enhancers and their connections to promoters

The study was published in the journal Nature Genetics.

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