Heterochromatin is a tightly packed form of DNA. Its major characteristic is that transcription is limited. As such, it is a means to control
gene expression, through regulation of the transcription initiation.
Chromatinis found in two varieties: euchromatinand heterochromatin. [cite journal
author = Elgin, S.C.
title = Heterochromatin and gene regulation in "Drosophila"
year = 1996
Curr. Opin. Genet. Dev.
issn = 0959-437X
volume = 6
pages = 193–202
doi = 10.1016/S0959-437X(96)80050-5] Originally, the two forms were distinguished cytologically by how darkly they stained - the former is lighter, while the latter stains darkly, indicating tighter packing. Heterochromatin is usually localized to the periphery of the nucleus.
Heterochromatin mainly consists of genetically inactive satellite sequences, [cite journal
author = Lohe, A.R., "et al."
title = Mapping simple repeated DNA sequences in heterochromatin of "Drosophila melanogaster"
year = 1993
journal = Genetics
volume = 134
issue = 4
pages = 1149–1174
issn = 0016-6731
url = http://www.genetics.org/cgi/content/full/134/4/1149
pmid = 8375654] and many genes are repressed to various extents, although some cannot be expressed in euchromatin at all. [cite journal
author = Lu, B.Y., "et al."
year = 2000
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
url = http://www.genetics.org/cgi/content/full/155/2/699
issn = 0016-6731
pmid = 10835392] Heterochromatin also replicates later in S phase of the cell cycle than euchromatin, and is found only in eukaryotes. Both
centromeres and telomeres are heterochromatic, as is the Barr bodyof the second inactivated X chromosomein a female.
Heterochromatin is believed to serve several functions, from gene regulation to the protection of the integrity of chromosomes; all of these roles can be attributed to the dense packing of DNA, which makes it less accessible to protein factors that bind DNA or its associated factors. For example, naked double-stranded DNA ends would usually be interpreted by the cell as damaged DNA, triggering
cell cyclearrest and DNA repair.Fact|date=June 2007Heterochromatin is generally clonally inherited; when a cell divides the two daughter cells will 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 different levels of expression from cell to cell, [cite journal
title=Gene silencing, cell fate and nuclear organisation
Curr. Opin. Genet. Dev.
issn=0959-437X] 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., "et al."
Insulatorsequences 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
author=Burgess-Beusse, B, "et al."
title=The insulation of genes from external enhancers and silencing chromatin
Proc. Natl Acad. Sci. USA
pmid=12154228] and loci in two "
Saccharomyces" spp. [cite journal
author=Noma, K., "et al."
title=transitions in distinct histone H3 methylation patterns at the heterochromatin domain boundaries
pmid=11498594] [cite journal
author=Donze, D. & R.T. Kamakaka
title=RNA polymerase III and RNA polymerase II promoter complexes are heterochromatin barriers in "Saccharomyces cerevisiae"
All cells of a given species will 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 chromosomecontain large regions of constitutive heterochromatin. In most organisms, constitutive heterochromatin occurs around the chromosome centromere and near telomeres.
Facultative heterochromatinThe regions of DNA packaged in facultative heterochromatin will not be consistent within the cell types of a species, and thus a sequence in one cell that is packaged in facultative heterochromatin (and the genes within poorly expressed) may be packaged in euchromatin in another cell (and the genes within no longer silenced). However, the formation of facultative heterochromatin is regulated, and is often associated with morphogenesisor differentiation. An example of facultative heterochromatin is X-chromosome inactivation in female mammals: one X chromosomeis packaged in facultative heterochromatin and silenced, while the other X chromosome is packaged in euchromatin and expressed.
Among the molecular components that appear to regulate the spreading of heterochromatin include the
Polycomb-group proteinsand non-coding genes such as Xist. The mechanism for such spreading is still a matter of controversy. [Talbert PB, Henikoff S. Spreading of silent chromatin: inaction at a distance. Nat Rev Genet. 2006 Oct;7(10):793-803.]
Saccharomyces cerevisiae", or budding yeast, is a model eukaryoteand 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 RNAipathway. 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 RNAi-induced transcriptional gene silencing (RITS) complex and the RNA-directed RNA polymerase complex (RDRC), are part of a 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 IIsynthesizes a transcript that serves as a platform to recruit RITS, RDRC and possibly other complexes required for heterochromatin assembly. 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 |chapterurl=http://www.horizonpress.com/rnareg|author= Vavasseur et al. |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|id= [http://www.horizonpress.com/rnareg ISBN 978-1-904455-25-7] ]
* Z. Avramova "Heterochromatin in Animals and Plants. Similarities and Differences". [http://www.plantphysiol.org/cgi/content/full/129/1/40 Plant Physiology] May 2002, Vol. 129, pp. 40-49.
* cite journal
author = Caron, H., "et al."
title = The Human Transcriptome
journal = Science
year = 2001
volume = 291
issue = 5507
pages = 1289–1292
doi = 10.1126/science.1056794
pmid = 11181992
Wikimedia Foundation. 2010.