AUG 23, 2016 12:38 PM PDT

Genes That "Stay Open For Business" Regulate Atherosclerotic Inflammation

WRITTEN BY: Kara Marker
Too much inflammation lies at the root of many diseases, one being atherosclerosis. In a new study from Michigan State University researchers are looking at when and how inflammatory genes are activated - how can we stop the immune system from unnecessarily activating these genes?

Atherosclerosis develops as a result of an ongoing inflammatory response: white blood cells aggregate, initiating the process of atherosclerotic plaque buildup, which scientists have seen in multiple studies including those with human participants. Then, a domino-type reaction occurs, where more and more cells continue to build up and cause blockages. Induced by a poor diet and other lifestyle factors, arterial endothelial cells start to express adhesion molecules on their surface that bind to white blood cells.

The Michigan State study looked at the expression of specific genes proven in the past to be related to the inflammatory pathway. With inflammation being strongly tied to atherosclerosis, which leads to various types of heart disease, understanding the process of how genes initially get involved in causing inflammation can help doctors can identify better drug targets and tackle the root of of the problem.

If it weren’t for the nucleosome, genes would constantly be available for activation, and the immune system (and certainly other systems) would run amuck. However, nucleosomes, the basic repeating structural and functional unit of chromatin, are present, and they inhibit gene access to the transcriptional enzymes that unzip and copy DNA. For opportune moments when genes should be activate, the body incorporates a nucleosome remodeler to make the genetic material available for transcription and “open for business.”

This research study is not so much about which genes are involved. Rather, the scientists were interested in identifying the specific steps of the mechanism that makes certain genes accessible during an infection. For example, if an individual’s immune system goes through the same steps during both an infection and when there is no warranted stimulus, the person is probably at risk for an autoimmune disease.
Floer, along with a graduate student and a research technician, describe their findings as a "cellular snowplow."
"What causes some cells to express these genes while other cells do not? Does the packaging of DNA play a role in deciding which genes are expressed?” asked lead author Monique Floer. “We believe that it's more about the regulation and the mechanics of how the transcriptional machinery is recruited than the genes themselves."

Specifically, Floer and her team isolated stem cells from the bone marrow of mice fighting infections and experiencing inflammation. The researchers grew the cells in the lab until they became full-fledged macrophages, what Nature Reviews Immunology call the “big eaters” of the immune system, for their tendency to clean up dead and dying cells as well as pathogens.

Floer described their findings like this: “As a cell differentiates into a specific cell type, it acquires all of the necessary information early on that dictates its behavior as an adult cell.” They saw that even as stem cells transitioned into adult macrophages, transcription factors and genes specific to the cell type began to bind, a process required to recruit the nucleosome remodeler, which the immune system would need later in case of an infection to “unlock” access to certain genes.

In the future, Floer and her team plan to extend their studies to the entire genome, addressing the following questions:
  • How will certain environmental changes occurring during stem cell differentiation change the amount of nucleosome remodelers that are recruited?
  • How might the absence of nucleosome remodelers “at a critical time in development” lead to cancer?

The present study was published in the Journal of Biological Chemistry.
 


Sources: Michigan State University, Circulation, Scitable by Nature Education
About the Author
  • I am a scientific journalist and enthusiast, especially in the realm of biomedicine. I am passionate about conveying the truth in scientific phenomena and subsequently improving health and public awareness. Sometimes scientific research needs a translator to effectively communicate the scientific jargon present in significant findings. I plan to be that translating communicator, and I hope to decrease the spread of misrepresented scientific phenomena! Check out my science blog: ScienceKara.com.
You May Also Like
JUL 19, 2018
Microbiology
JUL 19, 2018
Mom's Microbiome has a Big Impact on Kid's Autism Risk
For many years, scientists have been trying to learn more about the causes of autism....
AUG 04, 2018
Microbiology
AUG 04, 2018
The Viral Link to Irritable Bowel Disease
We now know of the importance of the microbiome, but most of the research focus has been on bacteria....
AUG 28, 2018
Cell & Molecular Biology
AUG 28, 2018
Finding the Source of a Common Immune Cell
Neutrophils are a highly abundant type of immune cell, outnumbering every other kind that runs through the bloodstream....
SEP 21, 2018
Immunology
SEP 21, 2018
Intrauterine Protection from Allergy Season
Pregnancies during allergy season may provide protection against allergy development in children...
OCT 31, 2018
Immunology
OCT 31, 2018
Masking the Pathogen
Researchers at Penn State have revealed bacterial pathogens capable of creating components used for DNA replication without the use of metal ions allowing them to evade the immune system...
NOV 05, 2018
Immunology
NOV 05, 2018
Amino Acid Helps to Promote T cells
Scientists at Vanderbilt show that the amino acid glutamine can contribute to a subset of T cell function and activation...
Loading Comments...