Identification of the tertiary structure of chromatin that regulates the immune response |

[팜뉴스=김태일 기자]Chromatin tertiary structures that regulate gene expression in dendritic cells that initiate immune responses have been identified.

Yonsei University College of Medicine Department of Tropical Medicine Professor Kim Hyung-pyo and Dr. Yang Bo-bae’s research team announced on the 4th that the chromatin tertiary structure affects the enhancer that regulates dendritic cell gene expression and regulates the human immune response.

The results of this study were published in the international journal Nature Communications (IF 17.694).

Dendritic cells initiate an immune response when the body initiates an inflammatory response. It recognizes not only pathogens such as bacteria, viruses, and parasites, but also cancer cells, and informs T cells, which are immune cells, to activate the immune function. Professor Ralph Steinman was awarded the Nobel Prize in Physiology or Medicine in 2011 for his discovery of dendritic cells.

Dendritic cells require gene expression to function properly. Enhancers determine the timing and location of these gene expression.

As it is known that enhancers can be affected by the external environment and regulate distant genes, finding out the location of the enhancer as well as the gene targeted by the enhancer has become an essential task to understand the regulation of gene expression.

The research team conducted experiments to identify enhancer information that targets gene expression in dendritic cells.

First, the tertiary structure of chromatin containing genes was analyzed. Dendritic cell DNA can reach two meters in length, but is contained in a cell nucleus that is only one hundred thousandth of a meter in diameter, regarding 10 micrometers. DNA exists in a folded state within the cell nucleus using a very elaborate pattern called chromatin tertiary structure. Chromatin tertiary structure has unique characteristics for each cell and regulates the activity of enhancers and gene expression according to external stimuli. The research team actually found that these complex chromatin tertiary structures influence enhancer activity.

Next, studies were conducted to identify enhancers that regulate dendritic cell gene expression in order to elucidate the process by which dendritic cells act when an inflammatory response occurs.

In order to identify target genes regulated by enhancers, an ‘enhancer network map’ was created using HiChIP technology. The enhancer network map is an in-depth analysis of the interactions between various chromatin tertiary structure components for all genes.

Through this, it was confirmed that even if the distance between the enhancer and the target gene is far, the chromatin tertiary structure change caused by the inflammatory response secures a close spatial location and affects the regulation of immune function as well as gene expression in dendritic cells.

In addition, by constructing mice deficient in the CTCF protein gene that determines the tertiary chromatin structure, they identified that the chromatin tertiary structure regulatory protein CTCF is essential for gene expression in dendritic cells.

Professor Kim Hyung-pyo said, “This study is the result of a 4-dimensional genome study that includes temporal changes in chromatin structure analysis in addition to genes beyond the level of genetic information that stores DNA sequences.” prepared,” he said.

Meanwhile, this research was supported by the National Research Foundation of Korea’s mid-sized research, biomedical technology development project, and Yonsei University College of Medicine’s intramural research funds.