Heterochromatin is a tightly packed form of DNA, which comes in different varieties. These
varieties lie on a continuum between the two extremes of constitutive and facultative heterochromatin.
Both play a role in the expression of genes, where constitutive heterochromatin can affect
the genes near them and where facultative heterochromatin is the result of genes that
are silenced through a mechanism such as histone deacetylation or piRNA through RNAi. Constitutive
heterochromatin is usually repetitive and forms structural functions such as centromeres
or telomeres, in addition to acting as an attractor for other gene-expression or repression
signals. Facultative heterochromatin is not repetitive and although it shares the compact
structure of constitutive heterochromatin, facultative heterochromatin can, under specific
developmental or environmental signaling cues, lose its condensed structure and become transcriptionally
active. Heterochromatin has been associated with the di and tri-methylation of H3K9 in
certain portions of the genome.
Structure Chromatin is found in two varieties: euchromatin
and heterochromatin. Originally, the two forms were distinguished cytologically by how intensely
they stained - the euchromatin is less intense, while heterochromatin stains intensely, indicating
tighter packing. Heterochromatin is usually localized to the periphery of the nucleus.
Despite this early dichotomy, recent evidence in both animals and plants 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, and many genes
are repressed to various extents, although some cannot be expressed in euchromatin at
all. Both centromeres and telomeres are heterochromatic, as is the Barr body of the second, inactivated
X-chromosome in a female. Function
Heterochromatin has been associated with several functions, from gene regulation to the protection
of the integrity of chromosomes; 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 DNA fragment such as by endonucleases in bacteria.
Some regions of chromatin are very densely packed with fibers displaying a condition
comparable to that of the chromosome at mitosis. Heterochromatin 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 at these boundary domains. This gives rise
to different levels of expression from cell to cell, which may be demonstrated by position-effect
variegation. Insulator sequences may act as a barrier in rare cases where constitutive
heterochromatin and highly active genes are juxtaposed.
Constitutive heterochromatin All cells of a given species that 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-chromosome contain large regions of constitutive heterochromatin.
In most organisms, constitutive heterochromatin occurs around the chromosome centromere and
near telomeres. Facultative heterochromatin
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 may be packaged in euchromatin in another cell. 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
include the Polycomb-group proteins and non-coding genes such as Xist. The mechanism for such
spreading is still a matter of controversy. Yeast heterochromatin
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, the rDNA, and the sub-telomeric regions. Fission yeast
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 RNAi-induced transcriptional
gene silencing complex and the RNA-directed RNA polymerase complex, 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. Both RNAi and
an exosome-dependent RNA degradation process contribute to heterochromatic gene silencing.
These mechanisms of Schizosaccharomyces pombe may occur in other eukaryotes. A large RNA
structure called RevCen has also been implicated in the production of siRNAs to mediate heterochromatin
formation in some fission yeast. See also
Centric Heterochromatin External links
Histology image: 20102loa - Histology Learning System at Boston University
References
Avramova Z. "Heterochromatin in Animals and Plants. Similarities and Differences". Plant
Physiology 129: 40–9. doi:10.1104/pp.010981. PMC 1540225. PMID 12011336.
Caron H, et al.. "The Human Transcriptome Map: Clustering of Highly Expressed Genes
in Chromosomal Domains". Science 291: 1289–92. doi:10.1126/science.1056794. PMID 11181992.