Epigenetics: ncRNAs and X-Chromosome Inactivation (3/3)

Published on 1 December 2025 at 12:00

In the final essay in this Epigenetics series the production and mode of action of non-coding RNAs are discussed and the three epigenetic mechanisms highlighted throughout this series – DNA methylation, histone modifications, and ncRNAs – are integrated in a discussion of the developmental event X-Chromosome Inactivation.

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Epigenetics: ncRNAs and X-Chromosome Inactivation

By Ashley Shipley

1 December 2025

 

1. Introduction

Throughout this essay series I have repeatedly made reference to the ‘expression of genes’ and how this process may be either enhanced or worsened by various epigenetic mechanisms. The ‘genes’ in question are simply sequences of DNA that may be used to create proteins. The first stage in the protein-making process, and the stage that can be affected by DNA methylation and histone modification, is the production of mRNA from the DNA, also called transcription. This messenger molecule is then used, through several more steps, to produce the protein that signifies the expression of the gene. These mRNA molecules are deemed protein-coding or simply coding RNAs. Interestingly, only a maximum of 2% of all of the RNA molecules within the cell can be deemed coding RNAs with the remaining 98% being non-coding RNAs (ncRNAs)1. For many years, the DNA sequences that encode these ncRNAs were seen as ‘junk DNA’ but, with more recent study, it has been acknowledged that, far from being useless components of the cell, ncRNAs may act as regulators for several stages of protein production. As briefly discussed in previous essays, ncRNAs may act as guides for the appropriate localisation of other epigenetic mechanisms prior to the transcription stage2, but they also have been shown to regulate subsequent stages such as post-transcription processing, where the mRNA is altered, and translation, where the mRNA is used to produce the amino acid, or early-protein, sequence3. The ability for ncRNAs to regulate the amount of protein produced from a gene places them firmly within the definition of epigenetic mechanisms and, as such, this series would not be complete without a discussion of the various types of ncRNAs. Therefore, the first two sections of this essay will be devoted to first small and then long ncRNAs, how they are produced and how they influence gene expression. The third and final section will essentially be a demonstration of how the different epigenetic mechanisms discussed in this series, namely DNA methylation, histone modifications, and ncRNAs, can work together to regulate the expression of an entire chromosome, an event termed X-Chromosome Inactivation.

 

2. Small Non-Coding RNAs

The first major class of ncRNAs are the small ncRNAs (sncRNAs or sRNAs), which are ncRNAs of approximately 20 to 30 base pairs long1. These sRNAs are typically transcribed as long RNA sequences from repetitive sequences throughout the DNA and are then processed through a number of steps to produce the smaller molecules4. Within the larger class of sRNA, there are different types of ncRNA, namely micro RNA (miRNA), small-interfering RNA (siRNA), and piwi-interacting RNA (piRNA), which are all produced in slightly different ways and have unique modes of action for the regulation of gene expression, although they are almost universally concerned with silencing genes1, whether it be through the targeting of other silencing epigenetic mechanisms such as DNA or histone methylation5 or direct interaction with the DNA/mRNA/proteins1.

 

2.1. Micro RNA (miRNA):

Mature miRNAs are single-stranded RNA molecules of 18-25 nucleotides in length. They are initially expressed, either with or without an accompanying mRNA, as long single-stranded pri-miRNAs. This molecule is then cleaved by the enzymes DROSHA and PASHA to create a short pre-miRNA, which contains the miRNA-unique hairpin-loop structure. The pre-miRNAs are transported from the nucleus to the cytoplasm of the cell where the hairpin-loop is cleaved by the enzyme DICER, producing a double-stranded mature miRNA. The double-stranded miRNA is bound by the RNA-induced silencing complex (RISC)-loading complex which separates the molecule into single stranded mature miRNAs and chooses one of the strands to retain within the mature RISC structure. RISC is then either kept within the cytoplasm or transported back into the nucleus to regulate the expression of mature mRNA or immature mRNA and DNA, respectively1, 6, 7.

The action of miRNA depends mainly on its target molecule but, as it is part of the RNA-induced silencing complex, the effect is typically to prevent the expression of genes through the targeting of any of the molecules involved in the several stages between DNA and protein. A major role of the miRNA strand within RISC is as a guide molecule to target RISC to a mature mRNA molecule within the cytoplasm, and the effect that RISC has on this molecule is determined by how well the miRNA binds to the mRNA. If the two sequences have perfect complementarity and therefore bind strongly to each other, the mRNA is cleaved by components of RISC, completely preventing its engagement in the translation stage of protein production and thereby silencing gene expression. If, however, the complementarity and binding is incomplete, the stability of the mRNA molecule is reduced, reducing but likely not completely obliterating its ability to be translated and thereby reducing but not altogether silencing gene expression1, 7. As this latter mechanism is likely to be the most prevalent of the two1 and up to 60% of all protein-coding genes are regulated by miRNAs8, miRNAs can be seen as an effective and widely used  way to subtly control the amount of protein produced from a specific gene. Apart from these well-researched modes of action, miRNAs may also play a role in activation of translation and transcription regulation through binding to DNA1.

There are several well-understood examples of gene regulation through miRNAs, especially in regard to development. One of the first miRNAs to be discovered in the nematode Caenorhabditis elegans and later in humans was let-7. This miRNA was shown to reduce the expression of Lin-28, a protein that is necessary for keeping the early embryo in a state of pluripotency, a state in which cells have the capacity to develop into any of the many different types of cells needed for the human body to function. This means that, when let-7 miRNA is expressed it binds to lin-28 mRNA, reducing its translation into the Lin-28 protein and so lifting the pluripotent state from the embryo and forcing the differentiation of different cell types, a process that is essential for the development of an organism. Let-7 expression is only activated when differentiation is commenced and a different suite of miRNAs that target anti-pluripotency genes are active during the pluripotent stage and are inactivated during the differentiation stage2. This shows that just as protein-coding genes are dynamically regulated in different cells and at different times during the life cycle, so are the non-coding sequences that aid in this regulation. The activation of miRNA molecules may be regulated by the same epigenetic mechanisms that regulate protein-coding genes and which have been discussed throughout this series, specifically DNA methylation and histone modifications9. miRNA genes can be found both within and between protein-coding genes so that when a protein-coding gene is transcribed so may the miRNA gene, essentially causing the miRNA to be regulated by the same mechanisms that regulate the protein-coding gene. Interestingly, however, the silencing of intergenic repetitive elements with corresponding activation of the protein-coding gene has been suggested as a potential consequence of epigenetic mechanisms throughout this series, meaning that miRNAs may not be transcribed along with the protein-coding gene, thereby increasing the expression of the protein. This complicated relationship between miRNA, mRNA, and other epigenetic mechanisms allows for the dynamic regulation of gene expression.

Epigenetic crosstalk is not simply one-way however as miRNAs also regulate the other epigenetic mechanisms. miRNAs, specifically miRNA-29 and miRNA-148, regulate DNA methylation through the altered expression of DNMT3b7, 10. If this leads to a reduction in DNMT3b expression, DNA methylation will also decrease due to the loss of its writer. As DNA methylation is commonly seen as a silencing mechanism, its loss will, instead of silencing genes, cause their activation, giving nuance to the action of miRNA. Similarly, miRNAs may target Polycomb Group genes, specifically EZH2, a component of the PRC2 complex which catalyses the methylation of H3K27, a histone mark that is associated with reduced gene expression9, 11, 12. The reduction of this silencing mark means that miRNA targeting leads to activation of the genes that would be typically silenced by H3K27 methylation. Finally, miRNA can bind to DNA and therefore act as a targeting mechanism for proteins such as chromatin-remodelling complexes which can change the expression of genes3.

 

2.2. Small-interfering RNA (siRNA):

Small-interfering RNAs (siRNAs) are sRNAs of a similar size to miRNAs but differ from them by being expressed from DNA as double-stranded molecules. From this different starting point, siRNAs go through the same processing and maturation stages as miRNAs, with the exception of the initial DROSHA cleavage stage, ending with the production of mature RISC. Additionally, the siRNA-RISC acts the same as miRNA-RISC in that the RNA molecule acts as a guide to localise the complex to complementary RNA, with perfectly complementary mRNA being cleaved and imperfectly complementary mRNA being destabilised and degraded. This similarity appears to end when considering the precise targets of miRNA and siRNA. Although both can be found within coding genes, miRNAs are unlikely to target the mRNA that they are expressed with while siRNAs preferentially target their neighbouring gene/mRNA1. Finally, siRNAs appear to have an even more important impact on DNA expression than miRNAs. siRNAs have been shown to target both DNA and histone methyltransferases13 and histone deacetylases3 to areas of the genome, typically areas from which they themselves were expressed1, in order to directly increase the epigenetic marks in the genome and silence specific genes.

 

2.3. Piwi-interacting RNA (piRNA):

Piwi-interacting RNAs (piRNAs) can reach a length towards the sRNA upper limit of approximately 30 nucleotides1, 13 and are involved in the silencing of the genome, particularly repetitive and transposable elements within the germline (egg and sperm cells and their precursors)10. However, both the production of piRNAs and their mode of action is quite different to that of miRNAs and siRNAs. For example, piRNAs are transcribed from a few clusters within the genome rather than from many places throughout the genome as is the case for the previous classes1. 13. As this likely leads to less control over precisely which piRNAs are expressed, piRNAs may constitute a more general silencing mechanism important for the protection of the genome instead of the gene-specific silencing perpetuated by miRNAs and siRNAs. As piRNAs are initially expressed in a cluster, the transcript must be processed into individual molecules. These mature piRNAs are then transported to the cytoplasm to interact with argonaut complexes comparable to RISC, in Drosophila melanogaster called Piwi or Aub. Piwi-piRNAs have a similar mechanism to RISC-mi/siRNAs as they move back into the nucleus and bind to complementary transposons to cleave and therefore silence dangerous transposon expression. Aub-piRNAs on the other hand stay within the cytoplasm to take part in the ‘ping-pong cycle’ which involves the cleavage of transposon transcripts that have been exported from the nucleus into smaller RNA molecules that can be used as piRNA molecules to enforce the silencing of the original, and therefore complementary, transposons1, 13. Like miRNA and siRNA, piRNA can also partake in epigenetic crosstalk with DNA methylation being targeted to transposons by these RNA molecules5.

 

3. Long Non-Coding RNAs (lncRNAs)

The second major class of ncRNAs is the long non-coding RNAs (lncRNAs). These single strand RNAs are generally over 200 nucleotides long and may either effect gene expression themselves or go onto produce sRNAs1. When they themselves alter gene expression it is typically through the recruitment of either epigenetic writers or transcription machinery giving lncRNAs a major role in coordinating the epigenetic crosstalk discussed throughout this essay series. Just as with sRNAs, there are several different types of lncRNAs but for this section I will cover just one: lincRNAs.

 

3.1. Large Intergenic Non-Coding RNAs (lincRNAs):

As suggested by their name, Large Intergenic Non-Coding RNAs (lincRNAs) are found between genes. When they are expressed, lincRNAs may interact with a variety of epigenetic enzymes that work to modify histones, typically in order to repress gene trancription5. PRC2, for example, is a major target for approximately 20% of lincRNAs9.  As discussed in Epigenetics: Histone Modifications and Chromatin Remodelling, PRC2 is a complex that tri-methylates H3K27, a mark that reduces the expression of the gene. It has been shown that the interaction between lincRNAs and PRC2, likely with lincRNA acting as a guide for the repressive complex to localise to specific part of the genome3, is imperative for effective silencing of the targeted gene9. This particular mode of action has been identified in X-Chromosome Inactivation which will be discussed in the next section1. PRC2 is not the only epigenetic modifier that can be bound by lincRNA. Indeed, KDM1A, a H3K4 demethylase, has also been found to interact with lincRNAs, indicating a role in the removal of activating marks and thereby repressing gene expression1. Furthermore, lincRNAs can alter gene expression more directly by either encouraging or discouraging the recruitment of transcription machinery to specific promoters, allowing the expression of certain genes and repressing that of others, particularly in response to environmental signals1, 10.  

Just like coding genes, active lincRNA genes are coated with activating histone modification such as H3K4me3 and H3K36me31 (see Epigenetics: Histone Modifications and Chromatin Remodelling for more details). The fact that the expression of lincRNAs is determined by the same epigenetic mechanisms that determine the expression of coding genes means that their population can be just as dynamically controlled depending on the environmental situation, leading to even more precise alterations in coding gene expression. These dynamics are a major reason why epigenetic crosstalk is so important in development and maintenance of the human body.

 

4. Combining Epigenetic Mechanisms - X-Chromosome Inactivation:

Now that the three main types of epigenetic mechanisms have been discussed in theory, it is time to move on to a discussion of how these mechanisms can be integrated in practice. A developmentally important epigenetic event is the inactivation of an X chromosome in individuals with more than one. Within every typical human cell, the genome is separated into 46 chromosomes, 22 pairs of autosomal chromosomes and 1 pair of sex chromosomes. Sex chromosomes come in two forms, the large X and the small Y, and are typically paired as two Xs or an X and a Y. Due to the different numbers of genes on the X and Y chromosomes, approximately 1000 on the X2 and 100 on the Y14, those who have more than one X chromosome, typically women, would show a greater expression of genes and their protein products, which is often lethal15. Therefore, a mechanism to compensate for this double dosage has evolved, namely the inactivation of all but one X chromosome. X-chromosome inactivation takes place very early in development, typically within the first month of development16, and can be broken down into four main stages: Counting, Choice, Initiation, and Maintenance.

    1. Counting

    The first step in X-chromosome inactivation is the counting of the number of X chromosomes present in the cell. This stage is incredibly important as development will likely be arrested if too many or too few X chromosomes are inactivated. Therefore, the cell must have a way of determining whether there is one, as in typical males, two, as in typical females, or more than two X chromosomes, as in atypical individuals, and of initiating the inactivation of all but one of these chromosomes. This stage is perhaps the least well understood of the entire process of X-chromosome inactivation, but it is likely that the X chromosomes physically touch each other, the contact focusing on a section of the chromosome referred to as the X-inactivation centre (XIC). If there is no contact made, that is a sign that there is only one X chromosome in the cell and so no inactivation is needed. If only one contact is made, there are two X chromosomes and so only one chromosome needs to be inactivated. If there is more than one contact made, there are more than two X chromosomes in the cell so more than one chromosome must be inactivated2, 3, 17.

    2. Choice

    The second step in this process is choosing which X chromosome to inactivate. In humans and indeed all placental mammals, this process has traditionally been defined as random with no preference for either the maternally or paternally inherited chromosome18. However, more recent research has indicated a possible bias, likely slight, towards the retention of the maternal X chromosome and the inactivation of the paternal one16. This has evolutionary precedent as marsupials, i.e. non-placental mammals, do tend to favour the paternally inherited chromosome for inactivation, and this is an example of genomic imprinting18, itself an epigenetic process that involves DNA methylation and ncRNAs to essentially label genes with their parent-of-origin and preferentially enhance or decrease the expression of said genes accordingly2.

    Regardless of whether the process is random or not, choosing which chromosome to inactivate, or perhaps more precisely which chromosome to leave active, begins with the expression of lncRNAs: XIST from the XIC domain of the chromosome previously discussed, and XACT from a location further along the chromosome. Both these lncRNAs are expressed from the genome starting as early as the four-cell stage, remain attached to the chromosome from which they were expressed, and are both initially found on all X chromosomes in the cell. From this point, what occurs can be described as a tug-of-war between the inactivating XIST and the activating XACT. It is likely that one chromosome will naturally express a slightly greater amount of either of the lncRNAs or other important factors, either randomly or due to genomic imprinting, and so will begin to accumulate a larger amount of XIST or XACT faster than its sister(s). As will be shown in the next section, XIST is fundamental to the silencing of the X chromosome and XACT has been shown to have an antagonistic relationship with XIST, preventing its spreading and subsequent silencing of the chromosome. Therefore, X chromosomes which express more XIST are more likely to be inactivated and chromosomes that express more XACT are more likely to prevent the action of XIST and remain active 2, 16.

    In cells with just one X chromosome, XIST expression is rapidly decreased in the first week of development16, likely due to repressive epigenetic mechanisms such as H3K9 and H3K27 methylation19, while cells with more than one X chromosome show XIST expression on all X chromosomes past this point16. This is an indication that counting has occurred by the first week of development, with cells that don’t require chromosome inactivation quickly reducing the level of XIST expression and those which do require inactivation continuing to express the important lncRNA. Over time in cells that do require inactivation, one chromosome will be covered in XACT and the remaining will be coated in XIST, setting the scene for the initiation of inactivation.

    3. Initiation

    Once XIST alone accumulates on the chromosome(s) to be inactivated, it spreads across the chromosome, avoiding genes that escape inactivation17 such as those that exist on both the X and Y chromosome 19. This coating of the X chromosome by XIST is a necessary initiation step in the inactivation of the chromosome as it produces a so-called ‘repressive compartment’ which essentially surrounds the genes to be inactivated and prevents the presence of important expression factors such as RNA polymerase II and transcription factors, thereby preventing the expression of these genes15. Furthermore, XIST acts as an anchor and a scaffold, tethering the X chromosome to the edge of the nucleus where it is less likely to associate with expression machinery and localising other epigenetic factors that carry out the inactivation of the chromosome17. The earliest of these epigenetic factors, namely those involved in histone modification, are deemed ‘dispensable’ for initiation of inactivation15 so the cascade of epigenetic modifications initiated by XIST accumulation can be seen as maintenance of the inactivated state, further condensing and decreasing the accessibility of the DNA.

    4. Maintenace

    Some of the first epigenetic enzymes to be recruited to the X chromosome through interaction with the XIST ncRNA are PRC1 and PRC2. As discussed in the previous essay, these are repressive complexes that bind to chromatin to deposit modifications on the histone proteins. Specifically, PRC2 trimethylates H3K27 and PRC1 ubiquitinates H2AK11917. Both of these modifications are ‘hallmarks’ of highly condensed and therefore inactivate DNA15, 16, and are invariably some of the earliest changes, alongside H3K9 and H4K20 methylation, H3K4 demethylation, and deacetylation of histones H3 and H4, in a cascade of modifications that characterise the inactivation of the X chromosome19. Both PRC1 and PRC2 can be recruited to the X chromosome through direct interaction with XIST, or through indirect methods such as interaction with each other or their modifications17.

    After the methylation and acetylation modifications of the histones are completed, histone H2A is replaced by the variant macroH2A which is an important contributor to gene silencing as it can prevent effective binding of transcription factors and nucleosome remodellers, silencing gene expression19. This is an important element of X chromosome inactivation maintenance as XIST has been shown to not be essential for maintenance of the inactive state15. By association, this suggests that the repressive compartment that excludes transcription factors and is created by the XIST RNA is not essential after initiation and is replaced by another mechanism, possibly the replacement of H2A with macroH2A.

    Up until this point, although relatively stable, X inactivation can be reversed as seen in the case of certain escape genes and during germ cell reprogramming19. This is generally prevented once the final ‘locking’ step of inactivation maintenance is completed: DNA methylation. Methylation of CpG islands within the promoter regions of inactivated genes occurs to prevent gene expression and enhance compaction of the chromatin, locking-in the inactive state and allowing it to be maintained through cell divisions2, 19. Furthermore, either the removal or prevention of methylation from the gene bodies occurs to produce a lower level of gene body methylation for the inactive X chromosome compared to the active one20. As gene body methylation is associated with increased gene expression, this further contributes to the silencing of the inactive genes.

       

        With the combination of ncRNAs, histone modifications, and DNA methylation, all but one X chromosome is inactivated within every cell in the human body. It is maintained over countless generations and ensures that individuals with more than one X chromosome do not receive damaging and potentially lethal doses of specific genes. The inactive X chromosome(s) becomes compacted into a Barr body18, is tethered towards the edge of the nucleus2, and is mostly transcriptionally silent, with the exception of the escaped genes previously mentioned. The active X chromosome remains generally free of the repressive modifications and compacted structure discussed above, maintains its position within the more central parts of the nucleus, and is mostly transcriptionally active, with the exception of the XIST gene18. The DNA sequences of the two chromosomes differ very slightly, only as much as those of any pair of chromosomes, and yet the way the cell treats them is vastly different and is maintained throughout the life of the organism. The reason for this: epigenetics.

         

        5. Conclusion

        The third and final major type of epigenetic modification is non-coding RNAs which interact with various protein-coding molecules, specifically DNA and mRNA, to regulate their expression. ncRNAs may further be seen as a modifier of epigenetic modifications as they have a role in the localisation of epigenetic enzymes and have been shown to regulate the expression of these enzymes. This shows how dynamic, nuanced, and complex epigenetic mechanisms are and how important crosstalk between different mechanisms is. This latter point is perfectly encapsulated in X-Chromosome Inactivation which is just one of many cellular events that require the integration of several epigenetic mechanisms to provide maintained regulation of gene expression, in this case over (most of) an entire chromosome.

        Throughout this essay series I have endeavoured to describe the three main types of epigenetic modification – DNA methylation, histone modifications, and ncRNAs – both individually and as a part of a complicated web of similar mechanisms. Epigenetic mechanisms may work to regulate others, as shown by lncRNAs, complement each other, as in DNA methylation and histone deacetylation, or compete with each other, as in contrasting activating and repressive histone methylation marks within the same nucleosome. These crosstalk mechanisms allow for highly nuanced gene expression regulation which allows genetically identically cells to form a great number of different cell types with unique functions and suite of activated genes. This ability allows for the production of complex tissues, organs, organ systems, and organisms. Essentially, organisms of a higher order than simple single cellular or identically celled multi-cellular organisms exist primarily due to epigenetic mechanisms and the evolution of complex mechanisms and crosstalk has paved the way for the production of highest order organisms such as humans.

         

        References

        1 Kaikkonen, M.U., Lam, M.T.Y. and Glass, C.K. (2011) ‘Non-coding RNAs as regulators of gene expression and epigenetics’, Cardiovascular Research, 90(3), pp. 430–440. Available at: https://doi.org/10.1093/cvr/cvr097.

        2 Nessa Carey (2012) The Epigenetics Revolution. UK: Icon Books Ltd.

        3 Inbar-Feigenberg, M. et al. (2013) ‘Basic concepts of epigenetics’, Fertility and Sterility, 99(3), pp. 607–615. Available at: https://doi.org/10.1016/j.fertnstert.2013.01.117.

        4 Felsenfeld, G. (2014) ‘A Brief History of Epigenetics’, Cold Spring Harbor Perspectives in Biology, 6(1), pp. a018200–a018200. Available at: https://doi.org/10.1101/cshperspect.a018200.

        5 Boskovic, A. and Rando, O.J. (2018) ‘Transgenerational Epigenetic Inheritance’, Annual Review of Genetics, 52, pp. 21–41. Available at: https://doi.org/10.1146/annurev-genet-120417-031404.

        6 Taby, R. and Issa, J.-P.J. (2010) ‘Cancer Epigenetics’, CA: A Cancer Journal for Clinicians, 60(6), pp. 376–392. Available at: https://doi.org/10.3322/caac.20085.

        7 Sato, F. et al. (2011) ‘MicroRNAs and epigenetics’, The FEBS Journal, 278(10), pp. 1598–1609. Available at: https://doi.org/10.1111/j.1742-4658.2011.08089.x.

        8 Moosavi, A. and Motevalizadeh Ardekani, A. (2016) ‘Role of Epigenetics in Biology and Human Diseases’, Iranian Biomedical Journal, (5), pp. 246–258. Available at: https://doi.org/10.22045/ibj.2016.01.

        9 Tammen, S.A., Friso, S. and Choi, S.-W. (2013) ‘Epigenetics: The link between nature and nurture’, Molecular Aspects of Medicine, 34(4), pp. 753–764. Available at: https://doi.org/10.1016/j.mam.2012.07.018.

        10 Gibney, E.R. and Nolan, C.M. (2010) ‘Epigenetics and gene expression’, Heredity, 105(1), pp. 4–13. Available at: https://doi.org/10.1038/hdy.2010.54.

        11 Pan, M.-R. et al. (2018) ‘Orchestration of H3K27 methylation: mechanisms and therapeutic implication’, Cellular and Molecular Life Sciences, 75(2), pp. 209–223. Available at: https://doi.org/10.1007/s00018-017-2596-8.

        12 Sharma, S., Kelly, T.K. and Jones, P.A. (2010) ‘Epigenetics in cancer’, Carcinogenesis, 31(1), pp. 27–36. Available at: https://doi.org/10.1093/carcin/bgp220.

        13 Fitz-James, M.H. and Cavalli, G. (2022) ‘Molecular mechanisms of transgenerational epigenetic inheritance’, Nature Reviews Genetics, 23(6), pp. 325–341. Available at: https://doi.org/10.1038/s41576-021-00438-5.

        14 Genome.gov (May 2024) ‘Y Chromosome Inforgraphic, National Human Genome Research Institute. Available at: https://www.genome.gov/about-genomics/fact-sheets/Y-Chromosome-facts (Accessed: 18 October 2025).

        15 Galupa, R. and Heard, E. (2018) ‘X-Chromosome Inactivation: A Crossroads Between Chromosome Architecture and Gene Regulation’, Annual Review of Genetics, 52(1), pp. 535–566. Available at: https://doi.org/10.1146/annurev-genet-120116-024611.

        16 Patrat, C., Ouimette, J.-F. and Rougeulle, C. (2020) ‘X chromosome inactivation in human development’, Development, 147(1), p. dev183095. Available at: https://doi.org/10.1242/dev.183095.

        17 Lu, Z., Carter, A.C. and Chang, H.Y. (2017) ‘Mechanistic insights in X-chromosome inactivation’, Philosophical Transactions of the Royal Society B: Biological Sciences, 372(1733), p. 20160356. Available at: https://doi.org/10.1098/rstb.2016.0356.

        18 Arthur M. Lesk (2012) Introduction to Genomics. 2nd edn. United States, New York: Oxford University Press.

        19 Chang, S., C. (2006) ‘Mechanisms of X-chromosome inactivation’, Frontiers in Bioscience, 11(1), p. 852. Available at: https://doi.org/10.2741/1842.

        20 Cotton, A.M. et al. (2015) ‘Landscape of DNA methylation on the X chromosome reflects CpG density, functional chromatin state and X-chromosome inactivation’, Human Molecular Genetics, 24(6), pp. 1528–1539. Available at: https://doi.org/10.1093/hmg/ddu564.

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