Scientists engineer synthetic DNA to study “architect” genes
Using synthetic DNA, the researchers created an artificial Hox cluster. The cluster is divided into two: active (to the left of the vertical line) and inactive (to the right), illustrating how Hox genes help cells know where they should be in the body. Credit: Pinglay et al., Science (2022)

Artificial Hox genes, which plan and direct where cells go to develop tissues or organs, have been created by researchers at New York University.

They found that clusters of Hox genes help cells remember where they are in the body.

The genes play a role in the body.

An anterior-posterior axis is a line that runs from head to tail in almost all animals. Hox genes determine the plan for where cells go along the axis and what body parts they make up. Hox genes make sure that organs and tissues are in the right place to form the thorax or wings.

Some cancers, birth defects, and miscarriages can be prevented if Hox genes fail.

The study's co-senior author said that he doesn't think we can understand development or disease without knowing Hox genes.

The Hox genes are difficult to study. There are only Hox genes in the piece of DNA where they are found and no other genes surrounding them. The Hox clusters have no repetitive elements. They are unique but difficult to study with conventional gene editing.

Synthetic DNA will be the new starting point.

Artificial Hox genes could be created to better study them.

We are very good at decoding genes. Small edits can be made in the genome thanks to the help of the CRISPR technology. We're not good at it. Writing or building new pieces of the genome can be used to find out what the smallest unit of the genome is needed for a cell to know where it is in the body.

Jef Boeke is the director of the Institute of System Genetics at the NYU school. Boeke's lab wanted to translate this technology to mammals.

Sudarshan Pinglay is a graduate student in Boeke's lab. The researchers delivered the DNA to the correct location. The researchers were able to differentiate between the synthetic rat DNA and the natural cells of mice using the different species.

'What I can't create, I don't understand,' said Dr. Richard Feynman. Boeke is the study's co-senior author and he said that they are now a giant step closer to understanding Hox

The Hox clusters are being studied.

The artificial Hox genes in mouse stem cells could be used to explore how Hox genes help cells to learn and remember. Regulatory regions that control how the Hox genes are activated are found in mammals. It was not known if the cluster alone or the cluster plus other elements was needed for the cells to remember where they are.

All of the information needed for cells to remember a signal is contained in these clusters. It's believed that the compact nature of Hox clusters is what helps cells learn their location.

Future research on animal development and human diseases can be done with the creation of synthetic genes.

Different species have different structures and shapes. A skate has no thorax and is just limbs while a snake has no thorax and is just limbs. It is possible that a better understanding of Hox clusters will help us understand how these systems are adapted to make different animals.

"This synthetic DNA technology, for which we have built a kind of factory, will be useful for studying diseases that aregenomically complicated and now we have a method for producing much more accurate models for them."

More information: Sudarshan Pinglay et al, Synthetic regulatory reconstitution reveals principles of mammalian Hox cluster regulation., Science (2022). DOI: 10.1126/science.abk2820. www.science.org/doi/10.1126/science.abk2820 Journal information: Science