Chromatin Looping

This web page was produced as an assignment for an undergraduate course at Davidson College.

Article Reviewed:
"The Shifting Nuclear Terrain: The human genome's architecture is a moving target"

What was the research project?

Technologies are emerging that are enabling research scientists to learn the affects that the three-dimensional shape of the genome (also known as the nucleome) has on cellular function and gene expression. Research teams have been attempting to make a three-dimensional and four-dimensional maps of the human genome and have been supported by the National Institutes of Health's 4-D Nucleome program, a $120 million effort to better "understand the principles behind the three-dimensional organization of the nucleus in space and time."

Were they testing a hypothesis or doing discovery science?

In the first project, they were doing discovery science as they attempted to map the human genome. For the second project, they were trying to identify the number of genes whose expression was changed with change in nucleome shape over time, which was testing a hypothesis.

What genomics technology was used in the project?

The main genomics technology that was used was Hi-C, a method which highlights the interactions between chromatin segments in a genome. This method essentially digests the DNA, breaking it up into small pieces before reattaching the segments that are spatially close (Lieberman-Aiden et al., 2009).
Another technique that was used was 3D fluorescent in situ hybridization, or 3D-FISH, a technique which fluorescently tags certain parts of DNA in three dimensions (Chen et al., 2015).

What is the take home message of the project?

The Hi-C technique was recently used by Rao et al. in an attempt to create a 3-D map of the human genome. In this project, they focused on identifying chromatin loops in the genome, and they found that the loops usually linked promoters and enhancers to the related genes (Rao et al., 2014). However, researchers are also now also trying to understand how the nucleome changes over time and what affects that has on gene expression and cellular function, thus the launching of the 4-D Nucleome program. One project used Hi-C and 3D-FISH to discover any links between gene expression and nucleome shape over time. They found that almost 2000 genes were affected as their expression and position changed in relation to other genes over time(Chen et al., 2015). These results also induce questions regarding earlier research on the nucleome, since some time-dependent chromatin loops may have been overrepresented or underrepresented.

What is your evaluation of the project?

The article was well written and was a good summary of the evolution of research projects involving the nucleome and how it affects cellular function and gene expression. I believe that these are important findings that will give direction to future studies in genomics.

Fig. 2 Explanation of the Hi-C Process. The linear section represents DNA segments that were in close proximity to one another in the sequence, whereas the two dots show areas that were brought together by chromatin loops. Information from S. Rao et al/Cell 2014; E. Lieberman-Aiden et al/Science 2009; image by E. Otwell.