Centric heterochromatin

Last updated
Mitoticchromosome Mitoticchromosome.png
Mitoticchromosome

Centric heterochromatin, a variety of heterochromatin, is a tightly packed form of DNA. Centric heterochromatin is a constituent in the formation of active centromeres in most higher-order organisms; the domain exists on both mitotic and interphase chromosomes. [1]

Heterochromatin A compact and highly condensed form of chromatin.

Heterochromatin is a tightly packed form of DNA or condensed DNA, which comes in multiple varieties. These varieties lie on a continuum between the two extremes of constitutive heterochromatin and facultative heterochromatin. Both play a role in the expression of genes. Because it is tightly packed, it was thought to be inaccessible to polymerases and therefore not transcribed, however according to Volpe et al. (2002), and many other papers since, much of this DNA is in fact transcribed, but it is continuously turned over via RNA-induced transcriptional silencing (RITS). Recent studies with electron microscopy and OsO4 staining reveal that the dense packing is not due to the chromatin.

DNA Molecule that encodes the genetic instructions used in the development and functioning of all known organisms and many viruses

Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development, functioning, and reproduction of all known organisms and many viruses. DNA and ribonucleic acid (RNA) are nucleic acids; alongside proteins, lipids and complex carbohydrates (polysaccharides), nucleic acids are one of the four major types of macromolecules that are essential for all known forms of life.

Interphase part of the cell cycle after quiescent phase and before cell division

Interphase is the phase of the cell cycle in which a typical cell spends most of its life. During this phase, the cell copies its DNA in preparation for mitosis. Interphase is the 'daily living' or metabolic phase of the cell, in which the cell obtains nutrients and metabolizes them, grows, reads its DNA, and conducts other "normal" cell functions. The majority of eukaryotic cells spend most of their time in interphase. This phase was formerly called the resting phase. However, interphase does not describe a cell that is merely resting; rather, the cell is living, and preparing for later cell division, so the name was changed. A common misconception is that interphase is the first stage of mitosis. However, since mitosis is the division of the nucleus, prophase is actually the first stage.

Centric heterochromatin is usually formed on alpha satellite DNA in humans; however, there have been cases where centric heterochromatin and centromeres have formed on originally euchromatin domains lacking alpha satellite DNA; this usually happens as a result of a chromosome breakage event and the formed centromere is called a neocentromere . [1]

Euchromatin A dispersed and relatively uncompacted form of chromatin.

Euchromatin is a lightly packed form of chromatin that is enriched in genes, and is often under active transcription. Euchromatin comprises the most active portion of the genome within the cell nucleus. 92% of the human genome is euchromatic.

Neocentromere

Neocentromeres are new centromeres that form at a place on the chromosome that is usually not centromeric. They typically arise due to disruption of the normal centromere. These neocentromeres should not be confused with “knobs”, which were also described as “neocentromeres” in maize in the 1950s. Unlike most normal centromeres, neocentromeres do not contain satellite sequences that are highly repetitive but instead consist of unique sequences. Despite this, most neocentromeres are still able to carry out the functions of normal centromeres in regulating chromosome segregation and inheritance. This raises many questions on what is necessary versus what is sufficient for constituting a centromere.

Centric heterochromatin domains are flanked by pericentric heterochromatin. [1]

See also

Related Research Articles

Chromosome DNA molecule containing genetic material of a cell

A chromosome is a deoxyribonucleic acid (DNA) molecule with part or all of the genetic material (genome) of an organism. Most eukaryotic chromosomes include packaging proteins which, aided by chaperone proteins, bind to and condense the DNA molecule to prevent it from becoming an unmanageable tangle.

Centromere

The centromere is the specialized DNA sequence of a chromosome that links a pair of sister chromatids. During mitosis, spindle fibers attach to the centromere via the kinetochore. Centromeres were first thought to be genetic loci that direct the behavior of chromosomes.

Karyotype chromosome configuration in a cell or species

A karyotype is the number and appearance of chromosomes in the nucleus of a eukaryotic cell. The term is also used for the complete set of chromosomes in a species or in an individual organism and for a test that detects this complement or measures the number.

Chromatid

A chromatid is one copy of a newly copied chromosome which is still joined to the original chromosome by a single centromere.

Satellite DNA consists of very large arrays of tandemly repeating, non-coding DNA. Satellite DNA is the main component of functional centromeres, and form the main structural constituent of heterochromatin.

Repeated sequences are patterns of nucleic acids that occur in multiple copies throughout the genome. Repetitive DNA was first detected because of its rapid re-association kinetics. In many organisms, a significant fraction of the genomic DNA is highly repetitive, with over two-thirds of the sequence consisting of repetitive elements in humans.

Constitutive heterochromatin constitutive heterochromatin domains are regions of DNA found throughout the chromosomes of eukaryotes.The majority is found at the pericentromeric regions of chromosomes, but is also found at the telomeres and throughout the chromosomes

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 repeats known as satellite repeats, minisatellite and microsatellite repeats, and transposon repeats. In humans these regions account for about 200Mb or 6.5% of the total human genome, but their repeat composition makes them difficult to sequence, so only small regions have been sequenced.

Micronucleus

Micronucleus is the name given to the small nucleus that forms whenever a chromosome or a fragment of a chromosome is not incorporated into one of the daughter nuclei during cell division. It usually is a sign of genotoxic events and chromosomal instability. Micronuclei are commonly seen in cancerous cells and may indicate genomic damage events that can increase the risk of developmental or degenerative diseases. Micronuclei form during anaphase from lagging acentric chromosome or chromatid fragments caused by incorrectly repaired or unrepaired DNA breaks or by nondisjunction of chromosomes. This incorrect segregation of chromosomes may result from hypomethylation of repeat sequences present in pericentromeric DNA, irregularities in kinetochore proteins or their assembly, dysfunctional spindle apparatus, or flawed anaphase checkpoint genes. Many micronucleus assays have been developed to test for the presence of these structures and determine their frequency in cells exposed to certain chemicals or subjected to stressful conditions.

The family of heterochromatin protein 1 (HP1) consists of highly conserved proteins, which have important functions in the cell nucleus. These functions include gene repression by heterochromatin formation, transcriptional activation, regulation of binding of cohesion complexes to centromeres, sequestration of genes to nuclear periphery, transcriptional arrest, maintenance of heterochromatin integrity, gene repression at the single nucleosome level, gene repression by heterochromatization of euchromatin and DNA repair. HP1 proteins are fundamental units of heterochromatin packaging that are enriched at the centromeres and telomeres of nearly all Eukaryotic chromosomes with the notable exception of budding yeast, in which a yeast-specific silencing complex of SIR proteins serve a similar function. Members of the HP1 family are characterized by an N-terminal chromodomain and a C-terminal chromoshadow domain, separated by a Hinge region. HP1 is also found at euchromatic sites, where its binding correlates with gene repression. HP1 was originally discovered by Tharappel C James and Sarah Elgin in 1986 as a factor in the phenomenon known as position effect variegation in Drosophila melanogaster.

RNA-induced transcriptional silencing (RITS) is a form of RNA interference by which short RNA molecules – such as small interfering RNA (siRNA) – trigger the downregulation of transcription of a particular gene or genomic region. This is usually accomplished by posttranslational modification of histone tails which target the genomic region for heterochromatin formation. The protein complex that binds to siRNAs and interacts with the methylated lysine 9 residue of histones H3 is the RITS complex.

Centromere protein B protein-coding gene in the species Homo sapiens

Centromere protein B also known as major centromere autoantigen B is an autoantigen protein of the cell nucleus. In humans, centromere protein B is encoded by the CENPB gene.

CENPA protein-coding gene in the species Homo sapiens

Centromere protein A, also known as CENPA, is a protein which in humans is encoded by the CENPA gene.

INCENP protein-coding gene in the species Homo sapiens

Inner centromere protein is a protein that in humans is encoded by the INCENP gene.

CENPC1 protein-coding gene in the species Homo sapiens

Centromere protein C 1 is a protein that in humans is encoded by the CENPC1 gene.

CBX5 (gene) protein-coding gene in the species Homo sapiens

Chromobox protein homolog 5 is a protein that in humans is encoded by the CBX5 gene. It is a highly conserved, non-histone protein part of the heterochromatin family. The protein itself is more commonly called HP1α. Heterochromatin protein-1 (HP1) has an N-terminal domain that acts on methylated lysines residues leading to epigenetic repression. The C-terminal of this protein has a chromo shadow-domain (CSD) that is responsible for homodimerizing, as well as interacting with a variety of chromatin-associated, non-histone proteins.

Segmental duplication are blocks of DNA ranging from 1 to 400kb in length which recur at multiple sites within the genome, sharing greater than 90% similarity. Multiple studies have found a correlation between the location of segmental duplications and regions of chromosomal instability. This correlation suggests that they may be mediators of some genomic disorders. Segmental duplications are shown to be flanked on both sides by large homologous repeats, which exposes the region to recurrent rearrangement by nonallelic homologous recombination, leading to either deletion, duplication, or inversion of the original sequence.

Nuclear organization

Nuclear organization refers to the spatial distribution of chromatin within a cell nucleus. There are many different levels and scales of nuclear organisation.

Robin Campbell Allshire is Professor of Chromosome Biology at University of Edinburgh and a Wellcome Trust Principal Research Fellow. His research group at the Wellcome Trust Centre for Cell Biology focuses on the epigenetic mechanisms governing the assembly of specialised domains of chromatin and their transmission through cell division.

References

  1. 1 2 3 Molecular Biology of the Cell. pp. 229–231. ISBN   978-0-8153-4105-5.