Heterochromatin

File:Heterochromatin vs. euchromatin.svg

Chromatin is found in two varieties: euchromatin and heterochromatin.

{{cite journal

| author = Elgin, S.C.

| title = Heterochromatin and gene regulation in Drosophila

| year = 1996

| journal = Current Opinion in Genetics & Development

| issn = 0959-437X

| volume = 6

| pages = 193–202

| doi = 10.1016/S0959-437X(96)80050-5

| pmid = 8722176

| issue = 2| url = https://openscholarship.wustl.edu/cgi/viewcontent.cgi?article=1213&context=bio_facpubs

| url-access = subscription

}}

Originally, the two forms were distinguished cytologically by how intensely they get stained – the euchromatin is less intense, while heterochromatin stains intensely, indicating tighter packing. Heterochromatin was given its name for this reason by botanist Emil Heitz who discovered that heterochromatin remained darkly stained throughout the entire cell cycle, unlike euchromatin whose stain disappeared during interphase.{{Cite journal |last1=Penagos-Puig |first1=Andrés |last2=Furlan-Magaril |first2=Mayra |date=2020-09-18 |title=Heterochromatin as an Important Driver of Genome Organization |journal=Frontiers in Cell and Developmental Biology |volume=8 |doi=10.3389/fcell.2020.579137 |doi-access=free |issn=2296-634X |pmc=7530337 |pmid=33072761}} Heterochromatin is usually localized to the periphery of the nucleus.

Despite this early dichotomy, recent evidence in both animals

{{cite journal | vauthors = van Steensel B | title = Chromatin: constructing the big picture | journal = The EMBO Journal | volume = 30 | issue = 10 | pages = 1885–95 | date = May 2011 | pmid = 21527910 | pmc = 3098493 | doi = 10.1038/emboj.2011.135 }}

and plants

{{cite journal | vauthors = Roudier F, Ahmed I, Bérard C, Sarazin A, Mary-Huard T, Cortijo S, Bouyer D, Caillieux E, Duvernois-Berthet E, Al-Shikhley L, Giraut L, Després B, Drevensek S, Barneche F, Dèrozier S, Brunaud V, Aubourg S, Schnittger A, Bowler C, Martin-Magniette ML, Robin S, Caboche M, Colot V | display-authors = 6 | title = Integrative epigenomic mapping defines four main chromatin states in Arabidopsis | journal = The EMBO Journal | volume = 30 | issue = 10 | pages = 1928–38 | date = May 2011 | pmid = 21487388 | pmc = 3098477 | doi = 10.1038/emboj.2011.103 }}

has suggested that there are more than two distinct heterochromatin states, and it may in fact exist in four or five 'states', each marked by different combinations of epigenetic marks.

Heterochromatin mainly consists of genetically inactive satellite sequences,

{{cite journal | vauthors = Lohe AR, Hilliker AJ, Roberts PA | title = Mapping simple repeated DNA sequences in heterochromatin of Drosophila melanogaster | journal = Genetics | volume = 134 | issue = 4 | pages = 1149–74 | date = August 1993 | doi = 10.1093/genetics/134.4.1149 | pmid = 8375654 | pmc = 1205583 | url = http://www.genetics.org/cgi/content/full/134/4/1149 }}

and many genes are repressed to various extents, although some cannot be expressed in euchromatin at all.

{{cite journal | vauthors = Lu BY, Emtage PC, Duyf BJ, Hilliker AJ, Eissenberg JC | title = Heterochromatin protein 1 is required for the normal expression of two heterochromatin genes in Drosophila | journal = Genetics | volume = 155 | issue = 2 | pages = 699–708 | date = June 2000 | doi = 10.1093/genetics/155.2.699 | pmid = 10835392 | pmc = 1461102 | url = http://www.genetics.org/cgi/content/full/155/2/699 }}

Both centromeres and telomeres are heterochromatic, as is the Barr body of the second, inactivated X-chromosome in a female.

File:General model for duplication of heterochromatin during cell division.svg

File:Heterochromatic versus euchromatic nuclei.jpg).]]

Heterochromatin has been associated with several functions, from gene regulation to the protection of chromosome integrity;

{{cite journal | vauthors = Grewal SI, Jia S | title = Heterochromatin revisited | journal = Nature Reviews. Genetics | volume = 8 | issue = 1 | pages = 35–46 | date = January 2007 | pmid = 17173056 | doi = 10.1038/nrg2008 | s2cid = 31811880 | url = https://zenodo.org/record/1233527 | quote = An up-to-date account of the current understanding of repetitive DNA, which usually doesn't contain genetic information. If evolution makes sense only in the context of the regulatory control of genes, we propose that heterochromatin, which is the main form of chromatin in higher eukaryotes, is positioned to be a deeply effective target for evolutionary change. Future investigations into assembly, maintenance and the many other functions of heterochromatin will shed light on the processes of gene and chromosome regulation. }}

some of these roles can be attributed to the dense packing of DNA, which makes it less accessible to protein factors that usually bind DNA or its associated factors. For example, naked double-stranded DNA ends would usually be interpreted by the cell as damaged or viral DNA, triggering cell cycle arrest, DNA repair or destruction of the fragment, such as by endonucleases in bacteria.

Some regions of chromatin are very densely packed with fibers that display a condition comparable to that of the chromosome at mitosis. Heterochromatin is generally clonally inherited; when a cell divides, the two daughter cells typically contain heterochromatin within the same regions of DNA, resulting in epigenetic inheritance. Variations cause heterochromatin to encroach on adjacent genes or recede from genes at the extremes of domains. Transcribable material may be repressed by being positioned (in cis) at these boundary domains. This gives rise to expression levels that vary from cell to cell,

{{cite journal | vauthors = Fisher AG, Merkenschlager M | title = Gene silencing, cell fate and nuclear organisation | journal = Current Opinion in Genetics & Development | volume = 12 | issue = 2 | pages = 193–7 | date = April 2002 | pmid = 11893493 | doi = 10.1016/S0959-437X(02)00286-1 }}

which may be demonstrated by position-effect variegation.

{{cite journal

|title=Cytogenetic and molecular aspects of position effect variegation in Drosophila melanogaster

|author=Zhimulev, I.F.

|date=December 1986

|journal=Chromosoma

|volume=94

|issue=6

|pages=492–504

|doi=10.1007/BF00292759

|s2cid=24439936

|issn=1432-0886|display-authors=etal|author-link=:ru:Жимулёв, Игорь Фёдорович

}}

Insulator sequences may act as a barrier in rare cases where constitutive heterochromatin and highly active genes are juxtaposed (e.g. the 5'HS4 insulator upstream of the chicken β-globin locus,

{{cite journal | vauthors = Burgess-Beusse B, Farrell C, Gaszner M, Litt M, Mutskov V, Recillas-Targa F, Simpson M, West A, Felsenfeld G | display-authors = 6 | title = The insulation of genes from external enhancers and silencing chromatin | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = Suppl 4 | pages = 16433–7 | date = December 2002 | pmid = 12154228 | pmc = 139905 | doi = 10.1073/pnas.162342499 | bibcode = 2002PNAS...9916433B | doi-access = free }}

and loci in two Saccharomyces spp.

{{cite journal | vauthors = Allis CD, Grewal SI | title = Transitions in distinct histone H3 methylation patterns at the heterochromatin domain boundaries | journal = Science | volume = 293 | issue = 5532 | pages = 1150–5 | date = August 2001 | pmid = 11498594 | doi = 10.1126/science.1064150 | s2cid = 26350729 }}

{{cite journal | vauthors = Donze D, Kamakaka RT | title = RNA polymerase III and RNA polymerase II promoter complexes are heterochromatin barriers in Saccharomyces cerevisiae | journal = The EMBO Journal | volume = 20 | issue = 3 | pages = 520–31 | date = February 2001 | pmid = 11157758 | pmc = 133458 | doi = 10.1093/emboj/20.3.520 }}

).

{{main article|Constitutive heterochromatin}}

All cells of a given species package the same regions of DNA in constitutive heterochromatin, and thus in all cells, any genes contained within the constitutive heterochromatin will be poorly expressed. For example, all human chromosomes 1, 9, 16, and the Y-chromosome contain large regions of constitutive heterochromatin. In most organisms, constitutive heterochromatin occurs around the chromosome centromere and near telomeres.

{{anchor|FacultativeHeterochromatin}}

File:Human karyotype with bands and sub-bands.png of a human, showing an overview of the human genome using G banding, which is a method that includes Giemsa staining, wherein the lighter staining regions are generally more euchromatic, whereas darker regions generally are more heterochromatic.{{further|Karyotype}}]]

The regions of DNA packaged in facultative heterochromatin will not be consistent between the cell types within a species, and thus a sequence in one cell that is packaged in facultative heterochromatin (and the genes within are poorly expressed) may be packaged in euchromatin in another cell (and the genes within are no longer silenced). However, the formation of facultative heterochromatin is regulated, and is often associated with morphogenesis or differentiation. An example of facultative heterochromatin is X chromosome inactivation in female mammals: one X chromosome is packaged as facultative heterochromatin and silenced, while the other X chromosome is packaged as euchromatin and expressed.

Among the molecular components that appear to regulate the spreading of heterochromatin are the Polycomb-group proteins and non-coding genes such as Xist. The mechanism for such spreading is still a matter of controversy.{{cite journal | vauthors = Talbert PB, Henikoff S | title = Spreading of silent chromatin: inaction at a distance | journal = Nature Reviews. Genetics | volume = 7 | issue = 10 | pages = 793–803 | date = October 2006 | pmid = 16983375 | doi = 10.1038/nrg1920 | s2cid = 1671107 }}

The polycomb repressive complexes PRC1 and PRC2 regulate chromatin compaction and gene expression and have a fundamental role in developmental processes. PRC-mediated epigenetic aberrations are linked to genome instability and malignancy and play a role in the DNA damage response, DNA repair and in the fidelity of replication.{{cite journal | vauthors = Veneti Z, Gkouskou KK, Eliopoulos AG | title = Polycomb Repressor Complex 2 in Genomic Instability and Cancer | journal = International Journal of Molecular Sciences | volume = 18 | issue = 8 | pages = 1657 | date = July 2017 | pmid = 28758948 | pmc = 5578047 | doi = 10.3390/ijms18081657 | doi-access = free }}

Saccharomyces cerevisiae, or budding yeast, is a model eukaryote and its heterochromatin has been defined thoroughly. Although most of its genome can be characterized as euchromatin, S. cerevisiae has regions of DNA that are transcribed very poorly. These loci are the so-called silent mating type loci (HML and HMR), the rDNA (encoding ribosomal RNA), and the sub-telomeric regions.

Fission yeast (Schizosaccharomyces pombe) uses another mechanism for heterochromatin formation at its centromeres. Gene silencing at this location depends on components of the RNAi pathway. Double-stranded RNA is believed to result in silencing of the region through a series of steps.

In the fission yeast Schizosaccharomyces pombe, two RNAi complexes, the RITS complex and the RNA-directed RNA polymerase complex (RDRC), are part of an RNAi machinery involved in the initiation, propagation and maintenance of heterochromatin assembly. These two complexes localize in a siRNA-dependent manner on chromosomes, at the site of heterochromatin assembly. RNA polymerase II synthesizes a transcript that serves as a platform to recruit RITS, RDRC and possibly other complexes required for heterochromatin assembly.{{cite journal | vauthors = Kato H, Goto DB, Martienssen RA, Urano T, Furukawa K, Murakami Y | title = RNA polymerase II is required for RNAi-dependent heterochromatin assembly | journal = Science | volume = 309 | issue = 5733 | pages = 467–9 | date = July 2005 | pmid = 15947136 | doi = 10.1126/science.1114955 | bibcode = 2005Sci...309..467K | s2cid = 22636283 }}{{cite journal | vauthors = Djupedal I, Portoso M, Spåhr H, Bonilla C, Gustafsson CM, Allshire RC, Ekwall K | title = RNA Pol II subunit Rpb7 promotes centromeric transcription and RNAi-directed chromatin silencing | journal = Genes & Development | volume = 19 | issue = 19 | pages = 2301–6 | date = October 2005 | pmid = 16204182 | pmc = 1240039 | doi = 10.1101/gad.344205 }} Both RNAi and an exosome-dependent RNA degradation process contribute to heterochromatic gene silencing. These mechanisms of Schizosaccharomyces pombe may occur in other eukaryotes.{{cite book |chapter-url=http://www.horizonpress.com/rnareg|author= Vavasseur|year=2008 |chapter=Heterochromatin Assembly and Transcriptional Gene Silencing under the Control of Nuclear RNAi: Lessons from Fission Yeast |title=RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity |publisher=Caister Academic Press |isbn=978-1-904455-25-7|display-authors=etal}} A large RNA structure called RevCen has also been implicated in the production of siRNAs to mediate heterochromatin formation in some fission yeast.{{cite journal | vauthors = Djupedal I, Kos-Braun IC, Mosher RA, Söderholm N, Simmer F, Hardcastle TJ, Fender A, Heidrich N, Kagansky A, Bayne E, Wagner EG, Baulcombe DC, Allshire RC, Ekwall K | display-authors = 6 | title = Analysis of small RNA in fission yeast; centromeric siRNAs are potentially generated through a structured RNA | journal = The EMBO Journal | volume = 28 | issue = 24 | pages = 3832–44 | date = December 2009 | pmid = 19942857 | pmc = 2797062 | doi = 10.1038/emboj.2009.351 }}

• Centric heterochromatin

== References ==

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• {{BUHistology|20102loa}}
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Category:Molecular genetics

Category:Nuclear organization