Heterochromatin and Euchromatin

Depending on the level of compactness, the chromatin gets divided into heterochromatin or euchromatin. The less compact one is known as the euchromatin. It forms an 11nm fiber, representing the nucleosome structure. The heterochromatin looks compact and dense. It is known as the 30 nm fiber. Let us discuss each one in details.

Euchromatin:

It involves the actively transcribing DNA of the chromosome. Thus, the euchromatin consists of normally functioning genes. It is a region of a eukaryotic chromosome that gets diffused during the interphase. The euchromatin consists of the active genomic form and stains lighter. Maximum percentage of the human genome involves the euchromatin (92%). Its structure appears like the beads on a string form. The nucleosomes comprise of proteins and DNA linked together. The proteins are known as histones. There are eight histones in the nucleosome. The methylated lysine 4 is present on the tail of the histone protein. It indicates a marker for the euchromatin.

Image 1: A chromosome with highlighted heterochromatin, euchromatin, and telomere

·        G-Banding: It involves the staining of the chromosome using a Giemsa stain. The stain helps in staining the regions of the DNA consisting of the very high amount of A-T base pairs. Euchromatin appears in the form of light bands after staining the chromosomes with Giemsa stain. Prokaryotes only show the presence of euchromatin and no heterochromatin.

Euchromatin actively involves the DNA undergoing transcription process. All euchromatin genes do not participate in the DNA to RNA processes. Mostly, the euchromatin gets transformed into the heterochromatin. It helps in controlling the gene expression and replication. The examples include the housekeeping genes. It encodes for the proteins involved in cell structure and function. Embryonic stem cells possess a diffused chromatin structure. The formation of condensed euchromatic varies in these cells. The condensation of the euchromatic differs from species to species.

Heterochromatinization of euchromatin: It is a form of repression of euchromatin. Sometimes a segment of a chromosome or the entire chromosome gets inactivated and condensed. It may also remain inactive for many generations. An example includes X inactivation in females. The human females possess two X chromosomes, out of which one gets inactivated. Meaning, certain genes on that particular X chromosome get inactivated. It is a crucial step for preventing lethality due to double dosage of alleles. 
Constitutive heterochromatin:

The constitutive heterochromatin regions occur throughout the chromosomes. Most of it occurs in the pericentromeric regions of the chromosomes. However, it also occurs in the telomeres or throughout the length of the chromosomes. Mainly, the chromosomes 1, 9, 16, 19, and Y consist of constitutive heterochromatin. It consists of tandem repeats such as satellite repeats, minisatellites, and microsatellites. Banding techniques help in visualizing the heterochromatin. Example of banding technique includes C banding. The regions having constitutive heterochromatin stain darker. The peripheral regions of the nucleus show a very high content of constitutive heterochromatin. The euchromatin occurs mostly in the center of the nucleus. Thus, it involves actively transcribing genes. It also manifests the segregation of sister chromatids.

The telomeric sequences involve a higher conservation rate as compared to that of the repeat sequences. Earlier, the biologists thought that the constitutive heterochromatin did not possess any genes. However, later on, total 450 genes got revealed in the Drosophila heterochromatin regions. Hence, they have highly condensed regions with epigenetic modifications. These modifications prevented transcription. The position effect occurs when the genes located near the constitutive heterochromatin get silenced. The replication of the constitutive heterochromatin occurs in the late S phase of the cell cycle. It does not participate in the meiotic recombination. The heterochromatin mainly gets condensed in the interphase and gets repressed transcriptionally. The condensation of the constitutive heterochromatin occurs due to histone modifications as well. The underacetylation of the histone H4 determines the overall status of the heterochromatin. Such modifications occur in both the mitosis and meiosis. Following are the modifications:

•        Histone hypoacetylation

•        Histone H3-Lys9 methylation

•        Cytosine methylation

Image 2: Difference between euchromatin and heterochromatin

Heterochromatin structure in the yeast telomere:

The telomeres are the cell protectors occurring at the end of the chromosomes. It gets packaged into tightly condensed heterochromatin. Not only does it condense tightly, but also extends into the adjacent regions. It prevents the lethal fusions with other chromosomes and protects the chromosomes from the action of nucleases. It helps in responding towards the DNA damage. The model organism for studying the heterochromatin involves budding yeast. It shows epigenetic inheritance of heterochromatin. An important gene in the budding yeast involved in the inheritance of heterochromatin is known as the ADE2 gene. It encodes an enzyme involved in adenine biosynthesis. Loss of the gene activity leads to an accumulation of a red pigment. If the gene moves in the vicinity to the telomeric heterochromatin region, the gene expression gets silenced leading to the synthesis of red pigment. The inheritance of the red pigment-producing genes remains stable due to the stability of the heterochromatin.

Centromeric heterochromatin:

The Centromeric sequences vary widely in different species. Normally, the chromosomes contain a single centromeric region containing the alpha satellite repeats. It gets packaged in the heterochromatin. Mitosis is an important phase of the cell cycle. During mitosis, centromere plays a crucial role in attaching the chromosome to the spindle microtubule. The chromosomal breaks lead to the growth of the fragment having the Centromeric region. A spontaneous inactivation of heterochromatin also leads to the formation of a monocentric chromosome.

Duplication of heterochromatin:

Special proteins in the heterochromatin show an ability to bind to the histones such as H3 or H4. These histones undergo a specific modification process. The enzyme responsible for the modification of histones also occurs in the heterochromatin region. The chromosome duplication leads to the random distribution of parent chromosomes into two daughter strands. Thus, it results in a mixture of old and new nucleosomes. The histone-modifying enzyme always binds to the old nucleosomes. The telomeric heterochromatin consists of three important Sir Proteins. They decide the duplication of the telomeric chromatin. The protein complexes under acetylates with the histone tails. It also shows its ability of binding with the other proteins.

References:

[1] Human Chromosomes, Orlando J. Miller, Eeva Therman, Page 71-72

[2] Heterochromatin: Molecular and Structural Aspects, Ram Sagar Verma

[3] Dictionary of Genetics, Himanshu Arora

[4] Essential Genetics: A Genomics Perspective, Daniel L. Hartl, Elizabeth W. Jones, Hartl Daniel

Copyright, 2019. All Rights Reserved.

A review on human chromosomes

An Introduction to chromosomes:

The ability of the chromosomes in getting stained reveals the true nature of the chromosome (derived from the Greek work word. The word chroma indicates color). These stainable bodies appear like threads under a microscope. They contain the genetic material, mainly the DNA coiled around the proteins. Human chromosomes are visible with when the cell is undergoing mitotic or meiotic cell division. There are total 46 chromosomes in each human cell.

·    Autosomes: There are total 44 autosomes or 22 pairs. Each pair consists of homologous chromosomes. In a pair, one chromosome comes from the father and the other chromosome comes from the mother.

·        Sex Chromosomes: There are two different types of sex chromosomes, X and Y respectively.

The average size of the human metaphase chromosome is 5 millimeters. Chromosomes tightly coil and get condensed during metaphase. Chromosomes appear in different shapes during each phase of the cell cycle. They appear thread-like during interphase. During metaphase, chromosomes look like rod-shaped. They look like V, J or rod-shaped during anaphase. Von Hartz coined the term chromosome. The scientists who first discovered the structure of chromosomes were Schleiden, Virchow, and Bütschli. Walter Sutton and Theodor Boveri independently developed the chromosome theory of inheritance in 1902.

An interphase nucleus contains strands of a material called chromatin. There are two regions in the chromatin, mainly coiled and extended regions.

·    Heterochromatin: It is the dark staining area of the chromatin. There are two types of heterochromatin. Constitutive heterochromatin contains repetitive sequences. It is present near the centromere. Constitutive heterochromatin never expresses itself. There is one more type of heterochromatin, known as facultative heterochromatin, which expresses itself.

·        Euchromatin: It is the light staining area of the chromatin.

The chief constituent of chromatin is DNA, the blueprint of life. At the time of cell division, chromatin strands coil into compact structures, so that they easily fit into the cell nucleus. Chromosomes appear as thick rods only during the cell division. They uncoil and form chromatin at the end of cell division.

Image: Human chromosomes revealed through karyotyping

Structure of the chromosome:

Metaphase chromosome appears clearly under the microscope. Following are the principal point to be discussed:

·        Chromatids: Each metaphase chromosome consists of two symmetrical halves parallel to each other. They are called chromatids. These chromatids are present in the form of chromonema during prophase. There are two types of chromatids mainly, sister and non-sister chromatids. Two chromatids are present on a single chromosome. Thus they are called sister chromatids. The concept of dyad describes a pair of sister chromatids. These structures join with the help of a centromere.  Non-sister chromatids are either of the two chromatids of a chromosome pair.

·        Centromere: A centromere is a light staining constricted area to which both the chromatids are attached. A centromere divides the chromatids into short and long arms respectively. The short arm is known as “p” arm. The long arm is known as “q” arm. Centromere produces a primary constriction. It is the position of the centromere. It is different for different chromosomes. Secondary constriction is also known as nucleolar organizer region. It is involved in the formation of the nucleolus. Human centromere consists of several hundred kilobases of repetitive DNA. Centromeres are the sites where spindle fibers are attached. Thus, centromere helps in the movement of the chromosome.

·     Satellite: A satellite is a region that is attached to the chromosome by a thread of chromatin. It is present at the distal region of the arm of the chromosome.

·        Telomere: A special DNA-protein complex is present at the ends of the chromosomes. This complex is known as a telomere, with tandem repeats of TTAGGG-3’ sequences between 3-20 kilobases in length. Telomeres are not genes since they do not code for any functional molecule. Telomeres provide structural stability to the chromosomes by sealing their ends. Telomeres protect the chromosomes from damage. They also protect the chromosome from fusing into a ring or binding to other DNA.

Classification of chromosomes:

1.     Classification based on the position of the centromere:  

·     Metacentric: The two arms are almost equal in their lengths. The location of the centromere is at the center of the chromosome.

·   Submetacentric: The two arms of the submetacentric chromosomes are unequal in length. The location of the centromere is slightly away from the center.

·   Acrocentric: One arm of an acrocentric chromosome is short. Whereas, the other arm is long.

·      Telocentric: A telocentric chromosome has only one arm.

2.     Standard classification: It is also known as Denver classification. It classifies chromosomes into seven groups, depending on the length of the chromosomes.

·  Group A: This group consists of pairs of chromosomes 1, 2 and 3. Chromosome 1 is the largest human chromosome. It represents 8% of the total DNA content.  Chromosome 2 is the second one. The third chromosome represents 6.5 % of the total DNA content.

·       Group B: This group consists of pairs of chromosome 4 and 5.

·    Group C: This group consists of pairs of chromosome 6, 7, 8, 9, 10, 11 and 12.

·        Group D: This group consists of pairs of chromosomes 13, 14 and 15.

·        Group E: This group consists of pairs of chromosomes 16, 17 and 18.

·        Group F: This group consists of pairs of chromosomes 19 and 20.

·        Group G: This group consists of pairs of chromosomes 21 and 22.

·  Sex Chromosomes: There are two types of sex chromosomes. X chromosome and Y chromosome are called sex chromosomes.

3.     Paris nomenclature: According to this method, the long and short arms of the chromosomes have specific regions that get stained. These regions are further stained using banding techniques. Such techniques may not only help to identify specific chromosomes, but also find out the location within the chromosome. Banding techniques may help to detect minor structural abnormalities.

What is sex chromatin?

The nucleus in the interphase is in the resting phase. An interphase nucleus shows a dark stain chromatin mass attached on one side of the nuclear membrane. Sex chromatin is also known as the Barr body. It is observed only in females. However, the chromatin determination using the Barr body is not as accurate as the Karyotyping technique.

What are chromosomal aberrations?

Chromosomal mutations or aberrations are variation in the normal chromosome structure or chromosome number.

A deletion is a chromosomal mutation in which a part of a chromosome is missing. Chromosomal breaks result in deletions. Sometimes an entire chromosome may get deleted. Duplication may lead to doubling of a chromosomal segment. Excision of a chromosomal segment follows reinsertion leading to an inversion. A translocation is a chromosomal mutation in which a chromosome segment gets positioned in a different location in the genome.

Chromosome Analysis:

Chromosome analysis indicates a proper diagnosis of many clinical conditions. It is a microscopic analysis of chromosomes in the dividing cells. Chromosomal analysis can detect chromosome number and structure.

Uses of chromosome analysis are as follows:

·        Detection of congenital malformations, mental retardation, and repeated abortions.

·        Prenatal diagnosis

·        Diagnosis of malignancies

Karyotyping:

Karyotyping is a test to evaluate the number and the structure of the chromosomes. In this procedure, the metaphase chromosomes are obtained and photographed. The procedure of karyotyping is specialized. Peripheral blood lymphocytes, bone marrow cells or amniotic fluid samples are collected and analyzed for chromosomes. A photo-micrograph reveals chromosomes scattered randomly. These chromosomes are arranged into groups, using the software. A karyotype can be sued to detect chromosomal abnormalities.

Chromosome Banding:

Analysis of chromosome becomes precise with the help of banding techniques. There are four types of banding techniques such as G-banding, Q-banding, R-banding, and C-banding. A unique pattern of light and dark bands are obtained using the G-banding technique.

Fluorescence in-situ hybridization (FISH):

FISH is a new diagnostic technique that involves a single-stranded probe annealing to its complementary sequence. FISH can be used to detect minute chromosomal aberrations, malignancies, and study of chromosomes.

References:
[1] Medical genetics, G.P. Pal
[2] Human Genetics, 3/e, Gangane
[3] Vogel and Motulsky's Human Genetics: Problems and Approaches, Friedrich Vogel, Gunter Vogel, Arno G. Motulsky
[4] Biology for the IB Diploma: Standard and Higher Level, Andrew Allott
[5] Principles of Medical Genetics, Thomas D. Gelehrter

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