What is Dr. Zubair Khalid's research focus?

Dr. Zubair Khalid specializes in molecular virology, mRNA vaccine development, and computational biology, with a focus on avian pathogens like IBDV and Avian Reovirus.

Where is Dr. Zubair Khalid currently working?

Dr. Zubair Khalid is a Postdoctoral Research Associate at the University of Maryland (UMD), specifically within the Department of Animal and Avian Sciences.

Gene Imprinting: How One Parent's Gene Wins the Expression Battle

By Dr. Zubair Khalid, DVM, MS, PhD · 2026-08-11

What Is Gene Imprinting?

Most of your roughly 20,000 protein-coding genes exist in two copies: one inherited from your mother and one from your father. For the vast majority of these genes, both copies are active, or "expressed," in your cells. But for a small subset—currently estimated at 100 to 200 genes in humans—only one copy is switched on. The other copy is silenced, not because it is mutated or damaged, but because of a chemical mark that records which parent it came from. This parent-of-origin-dependent expression pattern is called gene imprinting, and the genes involved are known as imprinted genes.

The term "imprinting" can be confusing because it is used in several biological contexts. In this context, it refers to a process that occurs in the germline—the cells that give rise to eggs and sperm—where a gene is "stamped" with a heritable mark that tells the developing embryo whether that gene came from the mother or the father. This mark is epigenetic, meaning it does not change the DNA sequence itself but alters how the DNA is read.

Definition and Key Terms

Gene imprinting (also called genomic imprinting) is an epigenetic phenomenon in which a gene is expressed in a parent-of-origin-specific manner. For an imprinted gene, the allele inherited from the mother may be active while the paternal allele is silent, or vice versa. The silenced allele is not deleted or mutated; it is simply turned off in a way that is remembered through cell divisions.

Key terms you will encounter:

Allele: One of two or more versions of a gene at a given position (locus) on a chromosome. You inherit one allele from each parent.
Epigenetic: Heritable changes in gene expression that do not involve changes to the DNA sequence itself.
Methylation: The addition of a methyl group (–CH₃) to a cytosine base in DNA, typically at a CpG dinucleotide (a cytosine followed by a guanine). This is the primary molecular mark of imprinting.
Imprinting Control Region (ICR): A specific DNA sequence that regulates the imprinting of one or more genes in a cluster. The ICR itself is differentially methylated—methylated on one parental chromosome and unmethylated on the other.
Monoallelic expression: Expression from only one allele, as opposed to biallelic expression from both.

Why It's Called 'Imprinting'

The term was coined in the 1960s and 1970s by mouse geneticists who noticed that certain chromosomal regions behaved differently depending on whether they came from the mother or the father. In 1984, two landmark experiments demonstrated that both parental genomes are required for normal mouse development. When researchers created mouse embryos with two copies of the maternal genome (parthenogenotes) or two copies of the paternal genome (androgenotes), both types of embryos failed to develop normally. The parthenogenotes had well-developed embryos but poor placentas, while the androgenotes had overgrown placentas but stunted embryos. This showed that maternal and paternal genomes are not functionally equivalent—something had "imprinted" them with different instructions.

The word "imprinting" evokes the idea of a stamp or seal being pressed into a material, leaving a permanent mark. In this case, the mark is a chemical modification to DNA and its associated proteins, and it is applied during gamete formation. Once the mark is in place, it is maintained through every subsequent cell division in the developing organism.

How Gene Imprinting Works: The Molecular Mechanism

The molecular basis of imprinting rests on three pillars: DNA methylation, histone modifications, and the action of insulator proteins. These components work together at specific regulatory sequences to ensure that one parental allele is expressed and the other is silenced.

DNA Methylation Marks

The central mark of imprinting is DNA methylation at cytosine bases. The enzyme family responsible for adding methyl groups is the DNA methyltransferases (DNMTs) . The key players are:

DNMT3A and DNMT3B: These are the de novo methyltransferases that establish new methylation patterns. During gametogenesis, DNMT3A, together with its cofactor DNMT3L, establishes methylation marks at imprinting control regions in a sex-specific manner. The oocyte (egg) and sperm each carry their own unique methylation patterns.
DNMT1: This is the maintenance methyltransferase. During DNA replication, DNMT1 recognizes hemimethylated DNA (where one strand is methylated and the new strand is not) and adds methyl groups to the new strand, preserving the imprint through cell divisions.

The methylation mark is placed at CpG dinucleotides—regions of DNA where a cytosine is followed by a guanine. These CpG-rich regions are called CpG islands, and when they are methylated, they typically lead to gene silencing.

Imprinting Control Regions (ICRs)

Imprinted genes are often found in clusters, and each cluster is regulated by a cis-acting element called an Imprinting Control Region (ICR) . An ICR is a stretch of DNA, typically 1 to 4 kilobases long, that is differentially methylated: it is methylated on one parental chromosome and unmethylated on the other. This differential methylation is established in the germline and is the primary determinant of imprinting.

There are two types of ICRs, named for which parental allele carries the methylation:

Paternally methylated ICRs: Methylated on the sperm-derived allele, unmethylated on the maternal allele.
Maternally methylated ICRs: Methylated on the egg-derived allele, unmethylated on the paternal allele.

The methylation status of the ICR determines whether it can bind regulatory proteins, which in turn controls the expression of nearby genes.

Reading the Imprint

The methylation mark itself does not directly silence genes. Instead, it is "read" by proteins that interpret the methylation status and translate it into changes in gene expression. Two key mechanisms are involved:

1. Insulator model (used by the IGF2-H19 locus): The unmethylated ICR can bind a protein called CTCF (CCCTC-binding factor). CTCF is a zinc-finger protein that acts as an insulator—it blocks the interaction between a gene promoter and its enhancer. When the ICR is unmethylated, CTCF binds and blocks the enhancer from activating the nearby gene. When the ICR is methylated, CTCF cannot bind, and the enhancer is free to activate the gene.

2. Promoter methylation model (used by many maternally methylated ICRs): When the ICR overlaps with a gene promoter, methylation directly prevents the binding of transcription factors and recruits proteins that compact the chromatin, silencing the gene. This is a more straightforward mechanism: methylated promoter = no transcription.

Additionally, histone modifications play a supporting role. Methylated DNA is often associated with histone H3 lysine 9 methylation (H3K9me3) and histone H3 lysine 27 methylation (H3K27me3), both of which are marks of silenced chromatin. Unmethylated, active regions are associated with histone acetylation and H3K4 methylation. These histone marks are established after DNA methylation and help maintain the silenced state.

The process of establishing and maintaining an imprint can be summarized in four steps:

Erasure: In the early embryo, before implantation, the genome undergoes widespread demethylation. Imprints from the previous generation are erased in the primordial germ cells (the cells that will become eggs and sperm).
Establishment: During gametogenesis, DNMT3A and DNMT3L establish new methylation marks at ICRs. The pattern depends on the sex of the parent: sperm establishes paternal marks, eggs establish maternal marks.
Maintenance: After fertilization, the zygote undergoes another round of demethylation, but the ICRs are protected from this global demethylation. Proteins like ZFP57 (zinc finger protein 57) bind to the methylated ICRs and recruit DNMT1 to maintain the methylation through cell divisions.
Reading: Throughout development, the methylation marks are interpreted by CTCF and other proteins, resulting in monoallelic expression.

Examples of Imprinted Genes in Humans and Mice

The best-studied imprinted genes come from mouse models and human genetic disorders. These examples illustrate the diversity of imprinting mechanisms and their biological consequences.

IGF2 and H19: A Classic Pair

The IGF2 (insulin-like growth factor 2) and H19 genes are located adjacent to each other on chromosome 11p15.5 in humans (chromosome 7 in mice). They are reciprocally imprinted:

IGF2 is expressed only from the paternal allele.
H19 is expressed only from the maternal allele.

This reciprocal pattern is controlled by a single ICR located between the two genes, called the H19/IGF2 ICR (also known as the imprinting control region 1, or ICR1). This ICR is paternally methylated.

The mechanism works as follows:

On the maternal chromosome, the ICR is unmethylated. CTCF binds to the ICR and acts as an insulator, blocking the downstream enhancer from interacting with the IGF2 promoter. As a result, IGF2 is silenced. The enhancer instead activates the H19 promoter, so H19 is expressed.
On the paternal chromosome, the ICR is methylated. CTCF cannot bind. The insulator is absent, so the enhancer can interact with the IGF2 promoter, activating IGF2. The H19 promoter is also methylated and silenced.

IGF2 is a growth factor that promotes cell proliferation and fetal growth. H19 produces a long non-coding RNA whose exact function is still under investigation, but it appears to act as a regulator of IGF2 and other genes. The net effect is that the paternal genome promotes growth, while the maternal genome restricts it—a theme that recurs throughout imprinting biology.

UBE3A and Angelman Syndrome

UBE3A (ubiquitin-protein ligase E3A) is an imprinted gene located on chromosome 15q11-q13. It encodes an enzyme that tags proteins for degradation via the ubiquitin-proteasome pathway. In most tissues, UBE3A is expressed from both alleles. However, in neurons, the paternal allele is silenced, and only the maternal allele is active.

The silencing of the paternal allele is mediated by a long non-coding RNA called SNHG14 (also known as UBE3A-ATS). This RNA is transcribed from the paternal chromosome in the antisense direction (from the opposite strand) and overlaps the UBE3A gene. The act of transcribing this antisense RNA leads to silencing of the paternal UBE3A allele, likely through the recruitment of chromatin-modifying enzymes that compact the DNA.

When the maternal allele is deleted or mutated, no functional UBE3A is produced in neurons, leading to Angelman syndrome. This condition is characterized by severe intellectual disability, seizures, absent speech, and a happy, excitable demeanor with frequent smiling and laughter. The disorder was first described by the pediatrician Harry Angelman in 1965.

Other Imprinted Genes

Beyond IGF2, H19, and UBE3A, there are many other imprinted genes with important functions:

Gene	Chromosome	Expressed Allele	Function	Associated Disorder
CDKN1C	11p15.5	Maternal	Cyclin-dependent kinase inhibitor; blocks cell cycle progression	Beckwith-Wiedemann syndrome (when mutated)
KCNQ1OT1	11p15.5	Paternal	Long non-coding RNA; silences neighboring genes	Beckwith-Wiedemann syndrome
SNRPN	15q11-q13	Paternal	Small nuclear ribonucleoprotein; involved in RNA splicing	Prader-Willi syndrome
GRB10	7p12	Maternal (in most tissues)	Growth factor receptor-bound protein; inhibits growth signaling	Russell-Silver syndrome
DLK1	14q32	Paternal	Transmembrane protein; involved in cell differentiation	Temple syndrome (maternal UPD 14)
MEG3	14q32	Maternal	Long non-coding RNA; tumor suppressor	Kagami-Ogata syndrome (paternal UPD 14)

This table is not exhaustive—there are more than 100 imprinted genes in humans—but it illustrates the range of functions and the clinical consequences of imprinting disruption.

Why Does Gene Imprinting Occur?

The existence of imprinting is paradoxical from an evolutionary standpoint. Why would an organism deliberately silence one copy of a gene, removing the protective redundancy that diploidy provides? If one allele is mutated, the imprinted gene has no backup. Several hypotheses have been proposed to explain the evolution of imprinting.

Parental Conflict Hypothesis

The most widely accepted explanation is the parental conflict hypothesis (also called the kinship theory), first proposed by David Haig in the 1980s. This hypothesis is rooted in the different reproductive strategies of males and females.

In mammals, the mother carries the fetus and provides all of the resources for its growth during pregnancy and lactation. The father's investment ends at conception. This creates a conflict:

The father's evolutionary interest is to extract as many resources as possible from the mother to ensure the survival and fitness of his offspring, even at the cost of the mother's future offspring (which may be fathered by other males).
The mother's evolutionary interest is to distribute resources evenly among all of her offspring, both current and future, to maximize her overall reproductive success.

According to this hypothesis, paternally expressed imprinted genes should promote fetal growth and resource extraction, while maternally expressed imprinted genes should restrict growth. This prediction is borne out by the data: IGF2 (paternally expressed) promotes growth, while H19 (maternally expressed) and CDKN1C (maternally expressed) restrict it. Mice with a disrupted paternal IGF2 allele are born 40% smaller than normal, while mice with a disrupted maternal CDKN1C allele show overgrowth.

The conflict hypothesis also explains why imprinting is most common in genes involved in growth, placentation, and brain development—all areas where the interests of mother and father diverge.

Coadaptation Hypothesis

A complementary hypothesis is the coadaptation hypothesis, which suggests that imprinting evolved to coordinate the expression of genes that function together in a pathway. By silencing one allele, the organism ensures that both copies of a gene come from the same parent, which may have co-evolved to work together.

For example, in the placenta, imprinted genes from the same parent may be co-expressed to ensure that their protein products interact properly. This hypothesis is less well supported than the conflict hypothesis but may explain the clustering of imprinted genes and the coordinated regulation of imprinted gene networks.

Another related idea is the maternal-offspring coadaptation hypothesis, which proposes that imprinting evolved to align the interests of the mother and her offspring. By silencing the paternal allele of certain genes, the mother can ensure that her offspring's gene expression matches her own, promoting cooperation rather than conflict.

It is important to note that these hypotheses are not mutually exclusive, and different imprinted genes may have evolved for different reasons. The conflict hypothesis remains the dominant framework, but it does not explain all imprinted genes—some imprinted genes have no obvious role in growth or resource allocation.

How Is Gene Imprinting Studied?

Studying imprinting requires distinguishing between the maternal and paternal alleles of a gene and determining which one is expressed. Several experimental approaches are used.

Allele-Specific Expression Assays

The most direct way to study imprinting is to measure allele-specific expression. This requires a way to distinguish the two parental alleles. The standard approach is to identify a single nucleotide polymorphism (SNP) in the gene of interest—a position where the maternal and paternal alleles differ by a single base.

The procedure is as follows:

Identify a heterozygous SNP: Sequence the gene in the individual or cell line of interest to find a SNP where the two alleles differ.
Extract RNA: Isolate total RNA from the tissue of interest.
Convert to cDNA: Use reverse transcriptase to convert the RNA to complementary DNA (cDNA).
Sequence or genotype the cDNA: Determine which SNP allele is present in the cDNA. If only one allele is detected, the gene is monoallelically expressed (imprinted). If both alleles are detected at roughly equal levels, the gene is biallelically expressed.

A more quantitative version of this assay uses RNA-seq (RNA sequencing) to measure the relative abundance of each allele across the entire transcriptome. This allows genome-wide identification of imprinted genes.

Methylation Analysis

Because DNA methylation is the primary mark of imprinting, measuring methylation at ICRs is a key diagnostic tool. The gold standard is bisulfite sequencing:

Treat DNA with sodium bisulfite: This chemical converts unmethylated cytosines to uracil, while methylated cytosines are protected and remain as cytosine.
PCR amplify the region of interest: The PCR reaction reads uracil as thymine, so unmethylated cytosines appear as thymines in the sequence.
Sequence the PCR product: Compare the sequence to the reference genome. Methylated cytosines appear as cytosines; unmethylated cytosines appear as thymines.

This method provides single-base resolution of methylation status. A related technique, pyrosequencing, is often used for quantitative methylation analysis at specific CpG sites. More recently, whole-genome bisulfite sequencing (WGBS) has been used to map methylation across the entire genome, allowing the identification of differentially methylated regions (DMRs) that mark imprinted loci.

Mouse Models

Mice are the primary model organism for studying imprinting because their imprinting patterns closely mirror those of humans. Several genetic tools are used:

Uniparental disomy (UPD): Mice are generated that inherit both copies of a chromosome (or a chromosomal region) from a single parent. If a gene in that region is imprinted, the UPD mouse will show abnormal expression—either double expression (if the gene is expressed from that parent) or no expression (if the gene is silenced from that parent). UPD mice have been used to map imprinted regions across the genome.
Knockout mice: Targeted deletion of an imprinted gene or an ICR reveals its function. For example, deleting the H19 ICR on the maternal chromosome leads to loss of imprinting and biallelic expression of IGF2, resulting in overgrowth.
Conditional knockouts: Using the Cre-loxP system, researchers can delete imprinted genes in specific tissues or at specific developmental stages, allowing them to study tissue-specific functions.

Imprinting and Human Disease

Errors in imprinting—whether through mutation, deletion, or abnormal methylation—lead to a range of human disorders. These conditions are often characterized by growth abnormalities, developmental delay, and neurological problems.

Prader-Willi and Angelman Syndromes

The most famous imprinting disorders are Prader-Willi syndrome (PWS) and Angelman syndrome (AS) , both caused by disruption of the imprinted region on chromosome 15q11-q13. This region contains both paternally expressed genes (including SNRPN and MAGEL2) and the maternally expressed gene UBE3A.

Prader-Willi syndrome results from the loss of function of paternally expressed genes in this region. This can occur through:
Deletion of the paternal 15q11-q13 region (about 70% of cases)
Maternal uniparental disomy (UPD), where the child inherits both copies of chromosome 15 from the mother (about 25% of cases)
Imprinting defects, where the paternal chromosome carries a maternal imprint (about 2-5% of cases)

PWS is characterized by severe hypotonia (low muscle tone) in infancy, poor feeding, and failure to thrive. In early childhood, this switches to hyperphagia (excessive hunger) and obesity, along with intellectual disability, short stature, and behavioral problems.

Angelman syndrome results from the loss of function of the maternally expressed UBE3A gene. This can occur through:
Deletion of the maternal 15q11-q13 region (about 70% of cases)
Mutation of the maternal UBE3A gene (about 10% of cases)
Paternal uniparental disomy, where both copies of chromosome 15 come from the father (about 2-5% of cases)
Imprinting defects (about 2-5% of cases)

AS is characterized by severe intellectual disability, absent speech, seizures, ataxia (lack of muscle coordination), and a distinctive happy demeanor with frequent laughter and smiling.

The fact that the same chromosomal region causes two different disorders depending on which parent contributes the abnormal chromosome is a powerful demonstration of imprinting in action.

Imprinting and Cancer

Imprinted genes are frequently dysregulated in cancer. The loss of imprinting (LOI) is a common event in tumorigenesis, where the normally silenced allele becomes reactivated, leading to biallelic expression.

The best-studied example is IGF2. Loss of imprinting at the IGF2-H19 locus leads to biallelic expression of IGF2, which promotes cell proliferation and survival. This is observed in many cancer types, including colorectal, breast, liver, and lung cancers. In colorectal cancer, LOI at IGF2 is present in about 30% of cases and is considered an early event in tumorigenesis.

Other imprinted genes with tumor suppressor functions, such as CDKN1C (which inhibits cell cycle progression) and MEG3 (a long non-coding RNA), are often silenced by hypermethylation in cancer. Conversely, imprinted oncogenes like IGF2 and DLK1 can be activated by loss of imprinting.

The role of imprinting in cancer has therapeutic implications. Because imprinted genes are expressed from only one allele, they are attractive targets for reactivation or silencing strategies. For example, drugs that inhibit DNA methyltransferases (such as 5-azacytidine) can reactivate silenced tumor suppressor genes, including imprinted ones.

Common Misconceptions and Pitfalls

When learning about imprinting, several misconceptions are common. Understanding these pitfalls will help you avoid them.

Imprinting vs. X-Inactivation

X-inactivation is the process by which one X chromosome in female mammals is randomly silenced to equalize gene expression between males (XY) and females (XX). While both X-inactivation and imprinting involve monoallelic silencing, they are fundamentally different:

X-inactivation is random: in each cell, either the maternal or paternal X chromosome is silenced, and the choice is made independently in each cell. The result is a mosaic of cells, some expressing the maternal X and some the paternal X.
Imprinting is deterministic: the silenced allele is always the same parent's allele, in every cell of the organism.

Additionally, X-inactivation silences nearly the entire X chromosome (about 800 genes), while imprinting affects only a small subset of autosomal genes.

Not All Genes Are Imprinted

Imprinting is the exception, not the rule. Only about 100-200 genes in humans are imprinted, representing less than 1% of the genome. The vast majority of genes are biallelically expressed. This is an important point because it means that for most genes, you have a functional backup copy if one allele is mutated.

Tissue-Specific Imprinting

Imprinting is not always permanent or universal across all tissues. Some imprinted genes show tissue-specific imprinting, where the gene is imprinted in some tissues but biallelically expressed in others. For example, UBE3A is imprinted only in neurons; in other tissues, both alleles are expressed. Similarly, GRB10 is imprinted in most tissues but biallelically expressed in the brain.

This tissue specificity is controlled by additional regulatory elements that can override the imprint in specific cell types. It also means that studying imprinting requires examining the tissue of interest, not just any cell type.

Imprinting Is Not Permanent Across Generations

Imprints are erased and re-established in each generation. During early embryonic development, the primordial germ cells undergo genome-wide demethylation, erasing the imprints inherited from the parents. New imprints are then established during gametogenesis, based on the sex of the individual. This means that an imprint is not a permanent feature of a gene—it is reset in every generation.

Summary and Key Takeaways

Gene imprinting is a fascinating example of how epigenetic mechanisms can produce parent-of-origin-specific gene expression. It challenges the assumption that both parental genomes are functionally equivalent and reveals the complex evolutionary forces that shape gene regulation.

The key points to remember are:

Imprinting is an epigenetic phenomenon where a gene is expressed from only one parental allele.
The molecular mark of imprinting is DNA methylation at imprinting control regions, established during gametogenesis and maintained through cell divisions.
Imprinted genes are often involved in growth and development, with paternally expressed genes promoting growth and maternally expressed genes restricting it.
The parental conflict hypothesis provides the leading evolutionary explanation for imprinting.
Disruption of imprinting leads to human disorders such as Prader-Willi syndrome, Angelman syndrome, and various cancers.
Imprinting is distinct from X-inactivation, affects only a small fraction of genes, and can be tissue-specific.

Frequently Asked Questions

What is gene imprinting?

Gene imprinting is an epigenetic phenomenon in which a gene is expressed from only one parental allele—either the maternal or the paternal copy—while the other allele is silenced. The choice of which allele is silenced is determined by chemical marks (primarily DNA methylation) that are established during egg and sperm formation.

How does gene imprinting work?

Gene imprinting works through DNA methylation at imprinting control regions (ICRs). During gametogenesis, specific ICRs are methylated in a sex-specific manner: some are methylated in sperm, others in eggs. After fertilization, these methylation marks are maintained through cell divisions by the enzyme DNMT1. The methylation status of the ICR determines whether regulatory proteins like CTCF can bind, which in turn controls the expression of nearby genes.

Can you give an example of gene imprinting?

The classic example is the IGF2-H19 locus on chromosome 11. IGF2 is expressed only from the paternal allele, while H19 is expressed only from the maternal allele. This reciprocal pattern is controlled by a single ICR that is methylated on the paternal chromosome. When the ICR is unmethylated (maternal), CTCF binds and blocks the enhancer from activating IGF2. When the ICR is methylated (paternal), CTCF cannot bind, and IGF2 is expressed.

Why does gene imprinting occur?

The leading explanation is the parental conflict hypothesis, which proposes that imprinting evolved because of the different reproductive interests of mothers and fathers. Fathers benefit from offspring that extract more resources from the mother, while mothers benefit from distributing resources evenly among all offspring. This conflict is reflected in the expression patterns of imprinted genes: paternally expressed genes tend to promote growth, while maternally expressed genes tend to restrict it.

What is the difference between gene imprinting and X-inactivation?

X-inactivation is the random silencing of one X chromosome in female mammals to equalize gene dosage between males and females. It is random—either the maternal or paternal X can be silenced in each cell. Imprinting is deterministic—the same parental allele is always silenced in every cell. X-inactivation silences most of an entire chromosome, while imprinting affects only a small number of individual genes.

What diseases are caused by imprinting errors?

Imprinting errors cause several human disorders, most notably Prader-Willi syndrome and Angelman syndrome, both caused by disruption of the imprinted region on chromosome 15. Loss of imprinting is also common in cancer, particularly at the IGF2 locus, where biallelic expression of this growth factor promotes tumorigenesis.

Is gene imprinting permanent?

Imprinting is stable within an individual's lifetime—the marks are maintained through every cell division. However, imprints are erased and re-established in each generation. During early embryonic development, the primordial germ cells erase all imprints, and new imprints are established during gametogenesis based on the sex of the individual. Additionally, some imprinted genes show tissue-specific imprinting, where the imprint is present in some tissues but not others.

Key Takeaways

Gene imprinting is a parent-of-origin-specific form of gene silencing, affecting only about 1% of human genes.
The molecular mechanism relies on DNA methylation at imprinting control regions, established in the germline and maintained by DNMT1.
Imprinted genes often regulate growth and development, with paternally expressed genes generally promoting growth and maternally expressed genes restricting it.
The parental conflict hypothesis is the leading evolutionary explanation for why imprinting evolved.
Disruption of imprinting causes human disorders including Prader-Willi syndrome, Angelman syndrome, and contributes to cancer.
Imprinting is distinct from X-inactivation: it is deterministic, not random, and affects individual genes rather than whole chromosomes.
Imprints are reset each generation and can be tissue-specific, making them a dynamic and complex layer of gene regulation.