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Genomic Imprinting

Q: At what stage of ontogenesis does the primary establishment of imprinting marks occur?

Selective methylation of Impr group genes occurs during germ cell development (gametogenesis, meiosis).

For medical students2 min readUpdated 2026-10-10

Genomic imprinting is an epigenetic mechanism in which a small group of genes (several dozen) maintains a stable "memory" of their parental origin. As a result, their expression depends directly on whether they were inherited from the mother or the father.

Impr GroupImprinted genes are designated with the special symbol Impr.

MechanismBased on selective DNA methylation leading to gene silencing.

Paternal GenesAbout 11 genes are active only in the male genome and develop extraembryonic structures.

Maternal GenesAbout 5 genes are active only in the female genome and form the embryo's body itself.

Context and Molecular Mechanism

The molecular events of genomic imprinting unfold against the background of the passive progression of a secondary oocyte (and subsequently the formed zygote) along the uterine tube toward the uterine cavity.

At the core of the phenomenon lies selective DNA methylation. This process involves the chemical addition of methyl groups to strictly defined genes of the Impr group. Methylation occurs in advance — during germ cell development (in the course of gametogenesis and meiosis).

The primary consequence of methylation is altered gene expression:

Methylated genes transition into an inactive state (are completely silenced).
Unmethylated genes of the same group, conversely, become actively transcribed.

A crucial feature of imprinting is its remarkable stability. Following fertilization, the assigned methylation status is reliably maintained in all somatic cells of the developing organism. With each cell division and DNA replication, the new nucleotide strand is methylated in strict accordance with the template of the old strand.

Functional Specialization of Parental Genomes

Genomic imprinting ensures a clear division of biological functions between chromosomes derived from the father and the mother. The presence of both genomes is critically important for normal development.

Genes Active in the Paternal Genome: This group includes approximately 11 genes. In maternal chromosomes, they are in a methylated (inactive) state, whereas in paternal chromosomes, they are active. Their primary task is to control the development of extraembryonic (provisional) organs necessary to sustain the embryo. Experimental Evidence: If a zygote is created containing exclusively two female pronuclei (complete absence of the paternal genome), development will begin. However, it inevitably halts due to critical underdevelopment of extraembryonic structures.

Genes Active in the Maternal Genome: This group consists of approximately 5 genes. In male chromosomes, they are silenced, while in female chromosomes, they are expressed. This group of genes dictates the development of the embryo's body itself. Experimental Evidence: When a zygote is artificially created with two male pronuclei (without the maternal genome), the reverse picture is observed: extraembryonic organs develop relatively normally, but the body of the embryo itself proves profoundly defective.

Reprogramming in Germ Cells

To transmit the correct imprinting pattern to the next generation, a mechanism of re-methylation (reprogramming) exists.

In the body's somatic cells, the initial distribution of paternal and maternal marks remains unchanged throughout life. However, in primordial germ cells (PGCs), a global reset occurs in two stages:

Demethylation. Methyl marks are removed from all Impr group genes. Information regarding both paternal and maternal marks is erased.
De Novo Methylation. Completely new marks are established that now strictly correspond to the genetic sex of the given individual. In spermatocytes, new marks are laid down according to the male pattern, and in oocytes, exclusively according to the female pattern.

Mnemonic

"Dad builds the house, mom raises the child": paternal genes (~11) are responsible for extraembryonic organs (the "house" for the embryo), while maternal genes (~5) are responsible for the embryo's body itself. In germ cells, the old house deeds are revoked (demethylation) and new ones are issued strictly according to the owner's sex.

Frequently asked questions

Which specific extraembryonic (provisional) organs develop thanks to the paternal genome?

Thanks to the paternal genome (the group of approximately 11 active genes), a complex of extraembryonic (provisional) organs develops, which are necessary to support embryogenesis. In early human embryogenesis, four key structures are formed:

Yolk sac (saccus vitellinus) — a temporary (regressing) organ.
Allantois — a temporary organ functioning in the first weeks of development.
Chorion — the permanent villous membrane.
Amnion — the permanent organ participating in the formation of fetal membranes.

What are the main genes subject to genomic imprinting in humans?

Genes subject to genomic imprinting are designated in sources by the general symbol Impr. It is also noted that about 80 imprinted genes have been identified in the human genome. Among the specifically named genes related to genomic imprinting disorders — Beckwith-Wiedemann syndrome — IGF2 and H19 are cited, localized in the 11p15 region.

Which genetic diseases occur due to impaired genomic imprinting?

Disorders of imprinted genes — such as microdeletions, uniparental disomies, or epigenetic labeling anomalies, including DNA methylation defects — lead to genomic imprinting diseases. Sources cite the following examples:

Prader-Willi syndrome — upon deletion of the 15q11–q12 chromosomal region inherited from the father.
Angelman syndrome — upon deletion of the same 15q region inherited from the mother.
Beckwith-Wiedemann syndrome — associated with the 11p15 region; manifestations include macroglossia and increased tumor predisposition.

In which cells is the methylation status preserved unchanged after fertilization?

The methylation status is stably preserved in all somatic cells of the new organism throughout its entire life.

What happens to an embryo in the absence of the maternal genome (two male pronuclei)?

Extraembryonic provisional organs develop relatively normally, but the embryo's body itself forms defective and non-viable.

At what stage of ontogenesis does the primary establishment of imprinting marks occur?

Selective methylation of Impr group genes occurs during germ cell development (gametogenesis, meiosis).

Why is demethylation necessary in primordial germ cells?

It is necessary to "reset" the old parental memory so that new marks (de novo) corresponding to the individual's own sex can then be established.

Go deeper

Topography and passive progression of secondary oocyte along the uterine tube during molecular reorganizations.
Biochemical bases of selective DNA methylation and the mechanism of gene expression silencing.
Features of DNA replication in somatic cells: copying methyl marks onto the new strand.
Molecular triggers of demethylation and de novo methylation in primordial germ cells.
Morphology of extraembryonic organs forming under the control of the paternal genome.