Heterochromatin: Structure and Function

Modified: 8th Feb 2020
Wordcount: 2876 words

Disclaimer: This is an example of a student written essay. Click here for sample essays written by our professional writers.
Any scientific information contained within this essay should not be treated as fact, this content is to be used for educational purposes only and may contain factual inaccuracies or be out of date.

Cite This



Heterochromatin is an important component of the eukaryotic nucleus. It has many important roles related to genetic silencing and the maintenance of genome stability. Heterochromatin is highly enriched with repetitive sequences, which can be repaired, silenced and sorted in a specialized manner. It is generally defined epigenetically by methylation of a specific histone H3 residue. Heterochromatin is characterized by its high compactness and its inhibitory effect on DNA transactions, such as gene expression (Zhang et al., 2013). This review will focus solely on the structure and function of heterochromatin, discussing three main factors; condensation of DNA, acetylation of histones and methylation of DNA. Relevant examples from a variety of eukaryotic cells will be used.


Genomic DNA in eukaryotic cells is packaged into chromatin; a structure which ultimately controls all nuclear processes involving DNA. This includes transcription, DNA replication and DNA repair. Heterochromatin is a genetically inactive form of chromatin typically found close to the nucleolus and the nuclear envelope. Its discovery was first made in 1928 by Emil Heitz when he observed differential chromosomal staining (Passarge, 1979). By this, he was able to clearly distinguish between two forms of chromatin (figure 1), which he named heterochromatin and euchromatin. The illustration of his observation shows a dark band and a light band; where the dark band represents heterochromatin and the light band represents euchromatin respectively. An important characteristic of heterochromatin that makes it so distinguishable from euchromatin is the fact that it remains highly condensed throughout the cell cycle. This allows the DNA contained in heterochromatin to be packed even more tightly and is why heterochromatin stains so much more intensely in comparison to euchromatin when using cytogenetic techniques. Both forms of chromatin have key roles in the transcription and expression of genes, however, they are both structurally and functionally different. This review will only focus on the structure and function of heterochromatin.

Get Help With Your Essay

If you need assistance with writing your essay, our professional essay writing service is here to help!

Essay Writing Service

Heterochromatin is also defined by its genetic silencing ability. This was identified by Muller in 1930, when he observed the effect of a mutation in Drosophila melanogaster (Muller, 1930). His results led him to hypothesize the closer a gene was to heterochromatin, the more likely it was to be silenced. Muller’s discover of position effect variegation (PEV) in Drosophila also helped to identify that PEV modifiers are needed to help regulate heterochromatin formation and function. These modifiers are responsible for H3K9 methylation and they also encode heterochromatin protein 1 (HP1).

Heterochromatin is sorted into two main categories: constitutive and facultative (Akiyama et al., 2015), however, some forms of heterochromatin overlap in characteristics of the two. Both forms of heterochromatin have very similar properties. These similarities include high condensation of heterochromatin, methylation of heterochromatin DNA, and late replication of heterochromatin DNA in comparison to euchromatin. Constitutive heterochromatin occurs at similar genomic regions in all cell types. On the other hand, facultative heterochromatin refers to the type of heterochromatin that can only be arranged at numerous chromosomal regions. These regions usually contain genes that must be kept genetically silent until they are needed to be expressed. The structure and function of both forms of heterochromatin will be discussed and compared in more detail throughout this review. 


Constitutive heterochromatin is a more stable form of heterochromatin in comparison with facultative heterochromatin in the sense that its condensation of DNA is irreversible. it usually forms at pericentromeric regions and at telomeres. These are gene-poor regions that are composed mainly of repetitive elements that are referred to as satellite DNA sequences. They can fold over on themselves and have an important role in maintaining chromosome stability. This is achieved by preventing inversion activity and regulating proper chromosomal regulation. Constitutive heterochromatin is defined epigenetically by trimethylation of the histone H3 at lysine 9 (H3K9). These histone marks are recognized by heterochromatin protein 1 (HP1), and upon its binding, chromatin conformation transitions to a more compact form (Nishibuchi and Déjardin, 2017). Presence of H3K9 implies it is responsible for the condensation of DNA. This compact form prevents the DNA contained within from being accessed, therefore preventing gene transcription. It is why heterochromatin is referred to as being genetically silent.



Facultative heterochromatin are highly conserved regions of DNA that can be converted into a euchromatic state, allowing them to become active and undergo transcription. This means that facultative heterochromatin has the potential for gene expression as its condensation of DNA is a reversible process, unlike that of constitutive heterochromatin. The most common example of facultative heterochromatin is the mammalian Barr body. Structure wise, facultative heterochromatin is enriched with LINE sequences. These sequences promote the spread of a condensed chromatin structure; heterochromatin. Facultative heterochromatin is found in gene-rich chromosomal regions unlike constitutive heterochromatin that is found in gene-poor areas (Jamieson et al., 2016). However, it is defined epigenetically by the same imprint as constitutive heterochromatin; trimethylation of histone H3 at lysine 9 (H3K9). Methylation of H3K9 occurs during the formation of the inactive X chromosome in somatic cells of female mammals (de Las Heras et al., 2003). Contrastingly, presence of H3K9 does not induce transcriptional silencing in facultative heterochromatin (Watts et al., 2018). It is actually achieved by HDAC-dependent deacetylation, although this process is not yet fully understood.


In eukaryotes, condensing chromosomal DNA into heterochromatin is important for gene silencing and proper chromosome segregation (Pikaard and Pontes, 2007). Heterochromatin is specifically marked by H2A.W, along with H3K9me2. One study concluded H2A.W was both necessary and sufficient for heterochromatin condensation in vivo (Yelagandula et al., 2014). The experiment undertaken suggested that H2A.W causes a higher order chromatin condensation. This was achieved by H2A.W promoting chromatin fiber-to-fiber interactions which ensured the bonds between chains were much stronger, making them harder to break. Moreover, chromatin condensation is vital for chromosome fortification from DNA mutilation. The high condensation results in the heterochromatin being strongly chromophillic and inaccessible to DNase 1 and other restriction enzymes. If the enzymes are unable to bind onto the DNA molecules, no gene-based reactions can commence, therefore rendering the DNA genetically silent. Heterochromatin is essential in ensuring gene regulation is as effective as it can be. By allowing the genetically silenced regions to be packed into dense heterochromatin structures, the active genes in euchromatin are more accessible. This makes the process of gene transcription more quick and efficient. Furthermore, due to the condensed nature of the heterochromatin structure, it was believed that gene silencing was achieved by limiting DNA access to transcription factors (Bi, 2014). However, further research proved that it is not the sole reason as to why heterochromatin is genetically inactive, but it does play a contributing role.


Hypoacetylation is the insufficient introduction of an acetyl group into a compound. It is usually a substitution of an acetyl group for an active hydrogen atom. It is important for chromatin compaction. Core histones are hypoacetylated in yeast heterochromatin. This suggests that nucleosomes are less “open” and induced to the formation of higher order structures (Bi, 2014). This is due to the fact that histones undergo post-transcriptional modification which affects the genetic activity of chromatin. The hypoacetylation of the histones, predominantly on the lysine, is associated with an inactive chromatin. The hypoacetylated status of histones within heterochromatin is facilitated by histone deacetylases (HDCAs) and is normally related to transcription repression.  Facultative heterochromatin is transcriptionally silenced by the deacetylation of a HDAC-dependent histone (Watts et al., 2018). The experiment was conducted using fission yeast Schizosaccharomyces pombe and managed to successfully prove that the HDACs were able to repress the transcription of the meiotic genes. However, it is not yet fully understood how HDACs manage to achieve this. Nonetheless, HDACs play an important role in the regulation of transcription, allowing the genes contained within the heterochromatin to be repressed at a transcriptional level. In Saccharomyces cerevisiae, heterochromatin is categorized by histone hypoacetylation and its association with silent information regulating (Sir) proteins. At the HM loci, the mating-type genes are bordered by cis-acting elements called silencers that encourage the development and conservation of heterochromatin. This is done by employing the SIR complex containing of Sir2, Sir3, and Sir4 proteins. Sir2 is a histone deacetylase that is accountable for keeping histones in heterochromatin in a hypoacetylated state (Bi, Ren and Kath, 2017). This emphasizes the view that the hypoacetylation of histones is important in effectively silencing the genetic information present in heterochromatin.


DNA methylation is a process by which methyl groups are added to a DNA molecule. It plays an important role in regulating heterochromatin (Yelagandula et al., 2014). DNA methylation and H3K9me2 work together to silence genes and are involved in the regulation of genome integrity and gene expression. The methylation of H3K9 is involved in the heterochromatinization of the genome. Methylated H3K9 is the target of heterochromatin protein 1 (HP1), an evolutionary conserved non-histone protein that is enriched at constitutive heterochromatin segments. A distinctive feature of the two heterochromatin types is the methylation of a specific histone H3 residue (Underwood et al., 2018). Constitutive heterochromatin is defined by trimethylation of lysine 9 of histone H3 (H3K9me3), whereas facultative heterochromatin is enriched in H3 lysine 27 trimethylation (H3K27me3). These histone marks on the histone H3 tails are recognized by specific reader proteins, and upon their binding, chromatin conformation transitions to a more compact form. Additionally, heterochromatin is hypomethylated at H3-K4 and K79. This allows SIR complexes – specialized silencing complexes – to specifically target heterochromatin nucleosomes (Bi, 2014). SIR complexes interact with hypoacetylated and hypomethylated nucleosomes. Research into methylation of histone H3 has proven it is also required in order for heterochromatin to effectively carry out its function of genetic silencing.


To conclude, heterochromatin is a form of chromatin in which the activity of genes is modified or suppressed. In short, its presence reveals that gene transcription is not taking place. This is due to its condensed structure, which does not allow regulatory proteins from accessing the DNA it contains, thus preventing gene transcription. Its structure is also related it to its maintenance of genome stability. The two main forms of heterochromatin differ in structure slightly, which allows them to be better suited to the role they play. Constitutive heterochromatin is permanently condensed. This is useful as it allows the focus of gene transcription to be focused on euchromatin. On the other hand, in facultative heterochromatin, the DNA is not condensed as densely, which allows the states to be interchangeable from heterochromatin and euchromatin. This allows important as it allows DNA to be accessed when it is needed. Moreover, the three structures of heterochromatin discussed in the review allow genomic silencing to be achieved. Condensation of DNA, acetylation of histones and methylation of histone H3 all contribute to heterochromatic function. Research does show we understand that heterochromatin regulates gene expression, however, its assembly is still poorly understood. Major factors of heterochromatin have so far been identified, however, their specific function at each heterochromatin locus remains unclear. Therefore, new strategies must be developed to uncover the mechanism of underlying heterochromatin organization.


  • Akiyama, T., Xin, L., Oda, M., Sharov, A.A., Amano, M., Piao, Y., Cadet, J.S., Dudekula, D.B., Qian, Y., Wang, W., Ko, S.B. and Ko, M.S. (2015) ‘Transient bursts of Zscan4 expression are accompanied by the rapid derepression of heterochromatin in mouse embryonic stem cells’, DNA research : an international journal for rapid publication of reports on genes and genomes, 22(5), pp. 307-318. doi: 10.1093/dnares/dsv013 [doi].
  • Bi, X. (2014) ‘Heterochromatin structure: Lessons from the budding yeast’, 66(10), pp. 657-666.
  • Bi, X., Ren, Y. and Kath, M. (2017) ‘Proliferating cell nuclear antigen (PCNA) contributes to the high-order structure and stability of heterochromatin in Saccharomyces cerevisiae’, Chromosome Research, 25(2), pp. 89-100. doi: 10.1007/s10577-016-9540-x.
  • de Las Heras, J., Sutherland, H., Gilbert, N., Allan, J., Boyle, S., Bickmore, W.A. and Jenuwein, T. (2003) ‘Formation of facultative heterochromatin in the absence of HP1’, The EMBO Journal, 22(20), pp. 5540-5550. doi: 10.1093/emboj/cdg520.
  • Jamieson, K., Wiles, E.T., McNaught, K.J., Sidoli, S., Leggett, N., Shao, Y., Garcia, B.A. and Selker, E.U. (2016) ‘Loss of HP1 causes depletion of H3K27me3 from facultative heterochromatin and gain of H3K27me2 at constitutive heterochromatin’, Genome Research, 26(1), pp. 97-107. doi: 10.1101/gr.194555.115.
  • Muller, H.J. (1930) ‘Types of visible variations induced by X-rays in Drosophila’, Journal of Genetics, 22(3), pp. 299-334. doi: 10.1007/BF02984195.
  • Nishibuchi, G. and Déjardin, J. (2017) ‘The molecular basis of the organization of repetitive DNA-containing constitutive heterochromatin in mammals’, Chromosome Research, 25(1), pp. 77-87. doi: 10.1007/s10577-016-9547-3.
  • Passarge, E. (1979) ‘Emil Heitz and the concept of heterochromatin: longitudinal chromosome differentiation was recognized fifty years ago.’, American Journal of Human Genetics, 31(2), pp. 106-115.
  • Pikaard, C. and Pontes, O. (2007) ‘Heterochromatin: condense or excise’, Nature Cell Biology, 9(1), pp. 19-20. doi: 10.1038/ncb0107-19.
  • Underwood, C.J., Choi, K., Lambing, C., Zhao, X., Serra, H., Borges, F., Simorowski, J., Ernst, E., Jacob, Y., Henderson, I.R. and Martienssen, R.A. (2018) ‘Epigenetic activation of meiotic recombination near Arabidopsis thaliana centromeres via loss of H3K9me2 and non-CG DNA methylation’, Genome research, 28(4), pp. 519-531. doi: 10.1101/gr.227116.117 [doi].
  • Watts, B.R., Wittmann, S., Wery, M., Gautier, C., Kus, K., Birot, A., Heo, D.H., Kilchert, C., Morillon, A. and Vasiljeva, L. (2018) ‘Histone deacetylation promotes transcriptional silencing at facultative heterochromatin’, Nucleic acids research, 46(11), pp. 5426-5440. doi: 10.1093/nar/gky232 [doi].
  • Yelagandula, R., Stroud, H., Holec, S., Zhou, K., Feng, S., Zhong, X., Muthurajan, U., Nie, X., Kawashima, T., Groth, M., Luger, K., Jacobsen, S. and Berger, F. (2014) ‘The Histone Variant H2A.W Defines Heterochromatin and Promotes Chromatin Condensation in Arabidopsis’, Cell, 158(1), pp. 98-109. doi: 10.1016/j.cell.2014.06.006.
  • Zhang, L., Chen, H., Bi, X. and Gong, F. (2013) ‘Detection of an altered heterochromatin structure in the absence of the nucleotide excision repair protein Rad4 in Saccharomyces cerevisiae’, Cell cycle (Georgetown, Tex.), 12(15), pp. 2435-2442. doi: 10.4161/cc.25457 [doi].


Cite This Work

To export a reference to this article please select a referencing style below:

Give Yourself The Academic Edge Today

  • On-time delivery or your money back
  • A fully qualified writer in your subject
  • In-depth proofreading by our Quality Control Team
  • 100% confidentiality, the work is never re-sold or published
  • Standard 7-day amendment period
  • A paper written to the standard ordered
  • A detailed plagiarism report
  • A comprehensive quality report
Discover more about our
Essay Writing Service

Essay Writing


Approximate costs for Undergraduate 2:2

1000 words

7 day delivery

Order An Essay Today

Delivered on-time or your money back

Reviews.io logo

1842 reviews

Get Academic Help Today!

Encrypted with a 256-bit secure payment provider