Chromosomal DNA and Its
Packaging in the Chromatin
Fiber
• The most important function of DNA is to carry genes, the
information that specifies all the proteins that make up an
organism—including information about when, in what types of cells,
and in what quantity each protein is to be made.
• The genomes of eukaryotes are divided up into chromosomes, and in
this section we see how genes are typically arranged on each
chromosome.
• In addition, we describe the specialized DNA sequences that allow a
chromosome to be accurately duplicated and passed on from one
generation to the next.
Challenge of DNA packaging
• Each human cell contains approximately 2 meters of DNA if
stretched end-to-end
• The nucleus of a human cell, which contains the DNA, is only
about 6 μm in diameter.
• This is geometrically equivalent to packing 40 km (24 miles) of
extremely fine thread into a tennis ball!
• The complex task of packaging DNA is accomplished by specialized
proteins that bind to and fold the DNA, generating a series of coils
and loops that provide increasingly higher levels of organization,
preventing the DNA from becoming an unmanageable tangle.
• Amazingly, although the DNA is very tightly folded, it is compacted
in a way that allows it to easily become available to the many
enzymes in the cell that replicate it, repair it, and use its genes to
produce proteins.
Eukaryotic DNA Is Packaged into a Set of Chromosomes
The display of the 46 human chromosomes at mitosis is called
the human karyotype.
22 autosomes and 2 sex chromosomes
Humans: 23 pairs
46 chromosome
Approximately 3.2 × 109 nucleotides
(in haploid set)
The sheer quantity of information provided by the
Human Genome Project is unprecedented in biology
Representation of the
nucleotide sequence
content of the human
genome
Molecular Biology of the Cell. 4th edition, Bruce Albert
LINES, SINES, retroviral-like elements, and DNA-only transposons are all mobile genetic
elements that have multiplied in our genome by replicating themselves and inserting
the new copies in different positions.
Simple sequence repeats are short nucleotide sequences (less than 14 nucleotide
pairs) that are repeated again and again for long stretches.
Segmental duplications are large blocks of the genome (1000–200,000 nucleotide
pairs) that are present at two or more locations in the genome.
Over half of the unique sequence consists of genes and the remainder is probably
regulatory DNA.
Most of the DNA present in heterochromatin, a specialized type of chromatin that
contains relatively few genes, has not yet been sequenced.
(1.5% of the entire human genome)
The Nucleotide Sequence
of the Human Genome
Shows How Genes Are
Arranged in Humans
Molecular Biology of the Cell. 4th edition, Bruce Albert
Few notable features of the human genome
• Average gene size of 27,000 nucleotide pairs
• Only about 1300 nucleotide pairs are required to encode a protein of
average size (about 430 amino acids in humans)
• The coding sequences are called exons; the intervening (noncoding)
sequences are called introns (long stretches of noncoding DNA)
• Each gene is associated with regulatory DNA sequences, which are
responsible for ensuring that the gene is expressed at the proper level
and time, and the proper type of cell. In humans, the regulatory
sequences for a typical gene are spread out over tens of thousands of
nucleotide pairs
Conserved and Nonconserved Regions of DNA Sequence
• The coding regions of the genome (the exons) are typically found in
short segments (average size about 145 nucleotide pairs) floating in a
sea of DNA whose exact nucleotide sequence is of little consequence
• Comparisons Between the DNAs of Related Organisms
• Distinguished sequences that have a function are conserved during
evolution, whereas those that are non-conserved are either free to
mutate randomly or are not present in all species.
Chromosomes Exist in Different States
Throughout the Life of a Cell
Faithful chromosome segregation requires the structural reorganization of
chromosomes into condensed metaphase chromosomes, which is needed for the
segregation of chromatids during anaphase. Conversely, chromosome decondensation
facilitates transcription and DNA replication
Molecular Biology of the Cell. 4th edition, Bruce Albert
(A) An electron micrograph showing
an enormous tangle of chromatin
spilling out of a lysed interphase
nucleus.
(B) A scanning electron micrograph
of a mitotic chromosome (more
condensed)
Chromatin: Complex of DNA, histones, and nonhistone proteins found in
the nucleus of a eucaryotic cell. The material of which chromosomes are
made. Molecular Biology of the Cell. 4th edition, Bruce Albert
Each DNA Molecule That Forms a Linear Chromosome Must
Contain a Centromere, Two Telomeres, and Replication Origins
A chromosome operates as a distinct structural unit: for a copy to be
passed on to each daughter cell at division, each chromosome must
be able to replicate, and the newly replicated copies must
subsequently be separated and partitioned correctly into the two
daughter cells.
These basic functions are controlled by three types of specialized
nucleotide sequence in the DNA, each of which binds specific
proteins that guide the machinery that replicates and segregates
chromosomes
Each chromosome has
multiple origins of
replication, one
centromere, and two
telomeres
Molecular Biology of the Cell. 4th edition, Bruce Albert
• The telomeres form special caps at each chromosome end
• The DNA replicates in interphase beginning at the origins of
replication and proceeding bidirectionally from the origins across
the chromosome
• The centromere also helps to hold the duplicated chromosomes
together until they are ready to be moved apart. (Kinetochore is the
protein complex at the centromere)
• Each chromosome consists of a single, enormously long linear
DNA molecule associated with proteins that fold and pack the
fine DNA thread into a more compact structure.
• The complex of DNA and protein is called chromatin (from the
Greek chroma, “color,” because of its staining properties).
• In addition to the proteins involved in packaging the DNA,
chromosomes are also associated with many proteins required
for the processes of gene expression, DNA replication, and DNA
repair.
DNA Molecules Are Highly Condensed in Chromosomes
All eukaryotic organisms have elaborate ways of packaging DNA into
chromosomes.
Recall: human chromosome 22 contains about 48
million nucleotide pairs.
Stretched out end to end, its DNA would extend about 1.5 cm.
Yet, when it exists as a mitotic chromosome, chromosome 22 measures
only about 2 μm in length, giving an end-to-end compaction ratio of
nearly 10,000-fold.
This remarkable feat of compression is performed by proteins that
successively coil and fold the DNA into higher and higher levels of
organization.
It is important to keep in mind that chromosome structure is
dynamic.
Not only do chromosomes globally condense in accord with the cell
cycle, but different regions of the interphase (G1, S and
G2) chromosomes condense and decondense as the cells gain access
to specific DNA sequences for gene expression, DNA repair, and
replication.
The packaging of chromosomes must therefore be accomplished in a
way that allows rapid localized, on-demand access to the DNA.
Nucleosomes Are the Basic Unit of Eukaryotic Chromosome Structure
The proteins that bind to the DNA to form eukaryotic chromosomes
are traditionally divided into two general classes: the histones and
the nonhistone chromosomal proteins.
The complex of both classes of protein with the nuclear DNA of
eucaryotic cells is known as chromatin.
Histones are responsible for the first and most basic level
of chromosome organization, the nucleosome, which was discovered
in 1974
(A) Chromatin isolated directly from an interphase nucleus appears in
the electron microscope as a thread 30 nm thick. (B) This shows a length
of chromatin that has been experimentally unpacked, or decondensed,
after isolation to show the nucleosomes.
Molecular Biology of the Cell. 4th edition, Bruce Albert
Molecular Biology of the Cell. 4th edition, Bruce Albert
Structural organization of the nucleosome.
https://www.chegg.com/
Each individual nucleosome core particle consists of a complex of
eight histone proteins—two molecules each of histones H2A, H2B,
H3, and H4—and double-stranded DNA that is 146 nucleotide pairs
long.
The histone octamer forms a protein core around which the double-
stranded DNA is wound.
Each nucleosome core particle is separated from the next by a
region of linker DNA, which can vary in length from a
few nucleotide pairs up to about 80.
On average, therefore, nucleosomes repeat at intervals of about
200 nucleotide pairs.
For example, a diploid human cell with 6.4 × 109 nucleotide pairs contains
approximately 30 million nucleosomes.
The formation of nucleosomes converts DNA molecule into a chromatin thread
about one-third of its initial length, and this provides the first level of DNA
packing.
The interface between DNA and histone is extensive: 142 hydrogen bonds
are formed between DNA and the histone core in each nucleosome.
Nearly half of these bonds form between the amino acid backbone of the
histones and the phosphodiester backbone of the DNA.
Numerous hydrophobic interactions and salt linkages also hold DNA
and protein together in the nucleosome.
For example, all the core histones are rich in lysine and arginine (two
amino acids with basic side chains), and their positive charges can
effectively neutralize the negatively charged DNA backbone.
The nucleosome core particle
consists of 146 base pairs
of DNA wrapped 1.65 turns
around a histone octamer
consisting of two molecules
each of H2A, H2B, H3, and
H4.
A chromatosome contains two
full turns of DNA (166 base
pairs) locked in place by one
molecule of H1 (Linker
histone)
https://www.microscopemaster.com/histones-and-their-functions.html
• The resulting 166 base pairs is not very long, considering that
each chromosome contains over 100 million base pairs of DNA on
average.
• Therefore, every chromosome contains hundreds of thousands of
nucleosomes, and these nucleosomes are joined by the DNA that
runs between them (an average of about 20 base pairs).
• This joining DNA is referred to as linker DNA.
• Each chromosome is thus a long chain of nucleosomes, which gives
the appearance of a string of beads when viewed using an electron
microscope
• A piece of DNA that is 1 meter long will become a "string-of-
beads" chromatin fiber just 14 centimeters (about 6 inches)
long.
• Despite this shortening, a half-foot of chromatin is still much too
long to fit into the nucleus, which is typically only 10 to 20
microns in diameter.
• Therefore, chromatin is further coiled into an even shorter,
thicker fiber, termed the "30-nanometer fiber," because it is
approximately 30 nanometers in diameter
The packaging of DNA into nucleosomes yields a chromatin fiber
approximately 10 nm in diameter. The chromatin is further
condensed by coiling into a 30-nm fiber, containing about six
nucleosomes per turn.
30-nm Fiber: Second level
• Involves the association of a string of nucleosomes into a fiber that is 30
nanometers.
• Depends on the linker histone protein H1 and nonhistone proteins.
• Two general models have been proposed for the structure of the 30-nm
fiber
https://books.byui.edu/genetics_and_molecul/13___chromosome_comp
Molecular biology of Cell, Watson 7th edition
Solenoid
The solenoid involves tight interactions between nucleosomes to form a
compact, symmetrical structure that resembles a cylinder. The solenoid
form of the 30-nm fiber is advantageous because it allows a high degree of
chromosome compaction; however, genes within the solenoid are not
accessible for transcription.
Zigzag
In the zigzag, nucleosome interaction is minimal and the linker regions are
free to bend and twist. As a result, the overall structure of the zigzag 30-nm
fiber is irregular. The zigzag form of the 30-nm fiber is advantageous
because it promotes the transcription of structural genes, but the degree of
chromosome compaction is not as great as with the solenoid form.
Recent evidence suggests that the zigzag form of the 30-nm fiber is
found predominantly in cells; however, some scientists believe that the two
forms of the 30-nm fiber can convert into each other depending on the
needs of the cell.
Radial Loop Domains (300-nm fibers): Third level
The third level of DNA compaction in eukaryotes involves the interaction
of the 30-nm fibers with nuclear matrix proteins to form radial loop
domains
Each radial loop consisting of
25,000–200,000 base pairs (bp)
of DNA
The nuclear matrix consists of
two parts, the nuclear
lamina and the internal nuclear
matrix.
https://books.byui.edu/genetics_and_molecul/13___chromosome_comp
The nuclear lamina portion of the nuclear matrix is composed of
cytoskeletal proteins and lies adjacent to the inner surface of the nuclear
membrane.
The internal nuclear matrix, which may include hundreds of different types
of proteins, forms a fine meshwork of filaments throughout the interior of
the nucleus.
DNA sequences called matrix-attachment regions (MARs) link the 30-nm
fiber to the internal nuclear matrix.
Anchoring the 30-nm fiber to the internal nuclear matrix results in the
formation of radial loop domains.
http://www.sivabio.50webs.com/preplication.htm
• Nucleosomes, 30nm fibers, and radial loop domains are
found in the chromatin of interphase cells.
• In contrast, during mitosis and meiosis, the chromosomes
become even more compacted—10,000 times more compact
than what is observed during interphase.
• In fact, the characteristic X-shaped chromosomes observed
in mitosis and meiosis are composed mainly of
heterochromatin. As a result, few structural genes are active
during mitosis and meiosis.
The 30-nanometer fiber
may be highly irregular
and not quite the
uniform structure
depicted in instructive
drawings
© 2013 Nature Education Adapted from Pierce,
Benjamin. Genetics: A Conceptual Approach, 2nd ed.
Chromatid formation : 4th Level
To form highly compacted mitotic and meiotic chromosomes, the
radial loops interact with a unique protein structure called
the scaffold.
The scaffold ensures that the radial loops throughout the majority of
the chromosome are in the heterochromatin state.
The structure of the scaffold is poorly understood; however,
scientists believe the scaffold is composed of nonhistone proteins,
including condensin, and nuclear matrix proteins.
The X-shaped metaphase chromosomes are produced by radial loop
domains binding to the scaffold.
1.Further compaction of radial loops to
form heterochromatin.
2.Formation of radial loop domains by
anchoring the 30-nm fiber to protein
fibers.
3.Wrapping of DNA around histone
proteins.
4.Metaphase chromosome with 2
copies of the DNA.
5.Formation of a 30-nm fiber via
histone H1 and other DNA-binding
proteins.
Next Chapter: Chromatin Remodeling
