![C-banding](https://upload.wikimedia.org/wikipedia/commons/9/95/C-banding.gif)
Constitutive heterochromatin domains are regions of DNA found throughout the chromosomes of eukaryotes.
The majority of constitutive heterochromatin is found at the pericentromeric regions of chromosomes, but is also found at the telomeres and throughout the chromosomes.
In humans there is significantly more constitutive heterochromatin found on chromosomes 1, 9, 16, 19 and Y.
Constitutive heterochromatin is composed mainly of high copy number
tandem repeat
Tandem repeats occur in DNA when a pattern of one or more nucleotides is repeated and the repetitions are directly adjacent to each other. Several protein domains also form tandem repeats within their amino acid primary structure, such as armadil ...
s known as satellite repeats,
minisatellite
A minisatellite is a tract of repetitive DNA in which certain DNA motifs (ranging in length from 10–60 base pairs) are typically repeated 5-50 times. Minisatellites occur at more than 1,000 locations in the human genome and they are notable for ...
and
microsatellite
A microsatellite is a tract of repetitive DNA in which certain DNA motifs (ranging in length from one to six or more base pairs) are repeated, typically 5–50 times. Microsatellites occur at thousands of locations within an organism's genome. ...
repeats, and
transposon
A transposable element (TE, transposon, or jumping gene) is a nucleic acid sequence in DNA that can change its position within a genome, sometimes creating or reversing mutations and altering the cell's genetic identity and genome size. Transpo ...
repeats. In humans these regions account for about 200Mb or 6.5% of the total
human genome
The human genome is a complete set of nucleic acid sequences for humans, encoded as DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual mitochondria. These are usually treated separately as the n ...
, but their repeat composition makes them difficult to sequence, so only small regions have been sequenced.
Visualization of constitutive heterochromatin is possible by using the
C-banding technique. The regions that stain darker are regions of constitutive heterochromatin.
The constitutive heterochromatin stains darker because of the highly condensed nature of the DNA.
Constitutive heterochromatin is not to be confused with
facultative heterochromatin
Heterochromatin is a tightly packed form of DNA or '' condensed DNA'', which comes in multiple varieties. These varieties lie on a continue between the two extremes of constitutive heterochromatin and facultative heterochromatin. Both play a rol ...
, which is less condensed, less stable, and much less
polymorphic, and which does not stain when using the C-banding technique.
Function
![Heterochromatin vs](https://upload.wikimedia.org/wikipedia/commons/f/f9/Heterochromatin_vs._euchromatin.svg)
Constitutive heterochromatin is found more commonly in the periphery of the nucleus attached to the nuclear membrane. This concentrates the
euchromatic DNA in the center of the nucleus where it can be actively transcribed. During mitosis it is believed that constitutive heterochromatin is necessary for proper segregation of sister chromatids and centromere function.
The repeat sequences found at the pericentromeres are not conserved throughout many species and depend more on
epigenetic
In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...
modifications for regulation, while telomeres show more conserved sequences.
Constitutive heterochromatin was thought to be relatively devoid of genes, but researchers have found more than 450 genes in the heterochromatic DNA of ''
Drosophila melanogaster
''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly" or "pomace fly". Starting with Ch ...
.''
These regions are highly condensed and epigenetically modified to prevent transcription. For the genes to be transcribed, they must have a mechanism to overcome the silencing that occurs in the rest of the heterochromatin. There are many proposed models for how the genes in these regions are expressed, including the insulation, denial, integration, exploitation, and TE restraining models.
When genes are placed near a region of constitutive heterochromatin, their transcription is usually silenced. This is known as
position-effect variegation Position-effect variegation (PEV) is a variegation caused by the silencing of a gene in some cells through its abnormal juxtaposition with heterochromatin via rearrangement or transposition. It is also associated with changes in chromatin conforma ...
and can lead to a
mosaic phenotype.
Replication and epigenetics
![General model for duplication of heterochromatin during cell division](https://upload.wikimedia.org/wikipedia/commons/e/e4/General_model_for_duplication_of_heterochromatin_during_cell_division.svg)
Constitutive heterochromatin is replicated late in
S phase
S phase (Synthesis Phase) is the phase of the cell cycle in which DNA is replicated, occurring between G1 phase and G2 phase. Since accurate duplication of the genome is critical to successful cell division, the processes that occur during ...
of the cell cycle and does not participate in meiotic recombination.
Histone modifications are one of the main ways that the cell condenses constitutive heterochromatin.
The three most common modifications in constitutive heterochromatin are
histone hypoacetylation,
histone H3-Lys9 methylation (H3K9), and
cytosine methylation
DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts t ...
. These modifications are also found in other types of DNA, but much less frequently. Cytosine methylation is the most common type, although it is not found in all eukaryotes. In humans there is increased methylation at the centromeres and telomeres, which are composed of constitutive heterochromatin. These modifications can persist through both mitosis and meiosis and are
heritable
Heredity, also called inheritance or biological inheritance, is the passing on of traits from parents to their offspring; either through asexual reproduction or sexual reproduction, the offspring cells or organisms acquire the genetic informa ...
.
SUV39H1 is a
histone methyltransferase
Histone methyltransferases (HMT) are histone-modifying enzymes (e.g., histone-lysine N-methyltransferases and histone-arginine N-methyltransferases), that catalyze the transfer of one, two, or three methyl groups to lysine and arginine residues of ...
that methylates H3K9, providing a binding site for
heterochromatin protein 1
The family of heterochromatin protein 1 (HP1) ("Chromobox Homolog", CBX) consists of highly conserved proteins, which have important functions in the cell nucleus. These functions include gene repression by heterochromatin formation, transcrip ...
(HP1). HP1 is involved in the chromatin condensing process that makes DNA inaccessible for transcription.
Diseases
Genetic disorders that result from mutations involving the constitutive heterochromatin tend to affect cell differentiation and are inherited in an autosomal recessive pattern.
Disorders include
Roberts syndrome
Roberts syndrome, or sometimes called pseudothalidomide syndrome, is an extremely rare autosomal recessive genetic disorder that is characterized by mild to severe prenatal retardation or disruption of cell division, leading to malformation of th ...
and
ICF syndrome.
Some cancers are associated with anomalies in constitutive heterochromatin and the proteins involved in its formation and maintenance.
Breast cancer
Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...
is linked to a decrease in the
HP1 alpha protein, while
non-Hodgkin's lymphoma
Non-Hodgkin lymphoma (NHL), also known as non-Hodgkin's lymphoma, is a group of hematological malignancy, blood cancers that includes all types of lymphomas except Hodgkin lymphomas. Symptoms include lymphadenopathy, enlarged lymph nodes, fever ...
is linked to hypomethylation of the genome and especially of satellite regions.
References
{{DEFAULTSORT:Constitutive Heterochromatin
DNA
Telomeres