The Importance of the Imprintome with Dr. Randy Jirtle

The idea of the impintome is still foreign to many people. So, let’s start with a simple explanation.

For the majority of genes, we inherit two functional copies—one from our mother and one from our father. However, imprinted genes follow a different pattern, as we inherit only one functional copy. Depending on the specific gene, either the copy from our mother or our father undergoes epigenetic silencing. This silencing process typically involves the addition of methyl groups during the formation of eggs or sperm.

The epigenetic modifications on imprinted genes typically stay put  throughout the organism's lifespan but undergo a reset during the formation of eggs and sperm. Regardless of their origin, certain genes are consistently silenced in eggs, while others are consistently silenced in sperm.

Soon after egg and sperm meet, most of the epigenetic tags that activate and silence genes are stripped from the DNA. However, in mammals, imprinted genes keep their epigenetic tags. Imprinted genes begin the process of development with epigenetic tags in place.

Imprinted genes are not the only genes that bypass epigenetic reprogramming in the early embryo. Studying imprinting may help researchers understand how other genes make it through reprogramming without losing their epigenetic tags.

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The field of epigenetics and the imprintome has grown exponentially in the past decade, largely fueled by Randy Jirtle's groundbreaking research.

Picture this: his 2003 study on how nutrition impacts gene regulation is the single most talked-about paper in the history of science. Jirtle's discoveries have been a game-changer, unraveling secrets about human health and the roots of diseases.

In this week's Everything Epigenetics podcast, I dive into a captivating conversation with Dr. Jirtle. We explore the fascinating intricacies of his research, unravel its profound implications for understanding disease development, and uncover the urgent call for more scientists to embark on the mesmerizing journey into the world of epigenetics.

In this Everything Epigenetics episode, you’ll learn about:
- Jirtle’s seminal 2003 Agouti mouse study
- The concept of imprinting and epigenetics
- The evolutionary biology approach
- How environmental and nutritional exposures can determine phenotypes through epigenetic regulation
- The profound impact that Jirtle had on the scientific community with his research
- How to identify imprintome regulatory regions in the germline
- The discovery of the full imprintome control regions in July 2022
- How to measure the imprintome with the imprintome array
- How the imprintome is starting to connect the dots to certain disease risks
- Future research on imprtinting and human evolution
- Challenges in researching the imprintome
- Pragmatic applications of the imprintome
- Excitement in current research

Where to find Randy:
Website: https://www.geneimprint.com

Dr. Randy Jirtle
Professor Randy L. Jirtle joined the Duke University Department of Radiology in 1977, and headed the Epigenetics and Imprinting Laboratory until 2012. He is now a Professor of Epigenetics in the Department of Biological Sciences at North Carolina State University, Raleigh, NC. Jirtle’s research interests are in epigenetics, genomic imprinting, and the fetal origins of disease susceptibility. He is known for his groundbreaking studies linking environmental exposures early in life to the development of adult diseases through changes in the epigenome, and for determining the evolutionary origin of genomic imprinting in mammals and the human imprintome.

In July of 2022, Dr. Jirtle and researchers from NC State published the full list of 1,488 hemi-methylated candidate ICRs in July 2022. This represents the first time in history that these imprint regulatory regions of the genome were fully identified in humans.

We are lucky enough to be working with him on the imprintome. In October of 2022, will all human ICRs identified, my company, TruDiagnostic, and North Carolina State University collaborated to create a custom methylation infinium microarray that can examine the entirety of the human imprintome. Furthermore, TruDiagnostic signed an exclusive license agreement to use and develop this microarray in further imprintome research.

We are now working with researchers worldwide to generate epigenetic health data using this new tool.

Dr. Randy Jirtle, thinks this represents a major step forward in our ability to predict disease risk. He even stasted in a press release with TruDiagnostic that “The identification of the human imprintome will allow scientists to determine - simply by sampling DNA from the blood or other accessible tissues - the role imprinted genes epigenetically altered by environmental exposures play in the formation of all diseases and behavioral disorders.”