Scientists and collaborators at the Van Andel Institute have identified a key part of the mechanism that processes genetic information before it is passed from parents to their children.
The results published today in the journal Science advancesThe new light sheds light on genomic imprinting, a basic biological process in which a gene from one parent is turned off while a copy from the other parent remains active. Errors in the printing process are linked to a range of diseases, such as the rare Silver Russell syndrome, as well as some types of cancer and diabetes.
Good temperament is critical to lifelong health, but despite its importance, we still lack a complete understanding of the factors that regulate this vital process. Our findings reveal the RNA mechanism that governs imprinting creation and explain why it differs between parents.”
Szabo Biroska, PhD, study author, associate professor at VAI
Our genetic information is encoded in DNA, a long, winding molecule that’s tightly packed to make up 23 pairs of chromosomes, half of which come from the father and half from the mother. Sperm and eggs contain only one 23 chromosomes -; Half of the genetic material needed for life. During fertilization, each contributes its half, resulting in a zygote containing a full set of 23 pairs of chromosomes.
But not all of the instructions in DNA are necessary at the same time or in the same places. This is where epigenetics comes into play. Epigenetic mechanisms suspend DNA with special chemical tags called methyl groups, which tell specific genes when they are active and when they are silent; All without changing the DNA sequence itself.
Imprinting occurs when methyl groups are added to specific genes during the formation of a sperm or egg. This, in turn, is important for determining which parental version of this gene is expressed in the offspring.
In order to better understand the processes that govern imprinting, Szabo and colleagues focused on the imprinting control region of DNA that regulates imprinting. Igf2 gene. Igf2 It plays key roles in fetal development and is only active on the chromosome inherited from the father. Very little methylation Internet Governance Forum2 The zonule of control in humans can lead to Silver Russell syndrome, which is characterized by reduced growth and an increased risk of metabolic disease.
“if it was Internet Governance Forum2 “The control region of the gene imprinting from the father is not methylated, and that can lead to disease,” Szabo said.
Using genetic models and in-depth genetic sequencing, the team found that methylation of L Igf2 The paternally inherited DNA control region undergoes a basic RNA-based process in the male germline.
“We previously found that RNA passes similarly through other imprinted regions with a paternal marker in male germ cells, suggesting that this same process is generally true for paternal imprinting,” Szabo said. “These results indicate a process that is applicable on a larger scale, which is exciting and will need to be confirmed in subsequent studies.”
Other authors include Ji Liao, Ph.D., Chen Fu, Ph.D., Evan Vanderkolk, Brianna M. Bucher, and Ken H. Lau, Ph.D., from VAI; Sangmin Song of the City of Hope Cancer Center; and Samuel Joscott, Ph.D., and Julie Brindamore, Ph.D., of the University of Montreal.
Van Andel Research Institute
Liao, J., et al. (2023) Establishment of the paternal methylation imprint in the control region of the H19/Igf2 imprint. Science advances. doi.org/10.1126/sciadv.adi2050.