NUCLEOSOMES, SOLENOID

CHROMATIN LOOPS, CHROMATIN

Reena Singh Chopra

BTY 107

Chromatin is a complex of macromolecules

found in cells, consisting of DNA, protein and

RNA.The primary functions of chromatin are 1) to
package DNA into a smaller volume to fit in the
cell, 2) to reinforce the DNA macromolecule to

allow mitosis, 3) to prevent DNA damage,

and 4) to control gene expression and DNA
replication.

Forms of Chromatin:
Euchromatin is a lightly packed form of
chromatin (DNA, RNA and protein)

Euchromatin comprises the most active portion

of the genome within the cell nucleus. 92% of the
human genome is euchromatic.

Heterochromatin is a tightly packed form of DNA, which comes in multiple

varieties.

Histones: Basic proteins. Play a major role in chromatin. They are present in the
chromatin of all eukaryotes in amounts equivalent to the amounts of DNA .
The major five histones are known as H1, H2A,H2B,H3 and H4. The molar ratio of
histones are 1H1, 2HA,2HB,2H3 and 2H4.

Composition of Histones

In eukaryotes, the DNA-protein complex, called chromatin is ordered into

higher structural levels than the DNA-protein complex in prokaryotes

Eukaryotic DNA
Is precisely combined with a large amount of
protein
Eukaryotic chromosomes

Contain an enormous amount of DNA

relative to their condensed length

Proteins called histones are responsible for the first level of DNA packing in
chromatin and bind tightly to DNA
The association of DNA and histones seems to remain intact throughout the cell
cycle

Nucleosomes: The histones specifically complexed with DNA to produce the basic structural
subunits of chromatin, small(approx. 110 Ao in diameter) ellipsoidal beadscalled nucleosomes.

Solenoid: The nucleosomes, and the DNA strands linking them, are packed closely together to
produce a 30nm diameter helix with about six nucleosome per turn. This is known as the 30nm

fibre, or the solenoid fibre.

It has a packing ratio of about 440, that 40um of DNA are packed into 1um length of
solenoid.

Nucleosomes (10-nm fiber)

In electron micrographs
Unfolded chromatin has the appearance of beads on a string
Each bead is a nucleosome: The basic unit of DNA packing
The next level of packing forms the 30-nm chromatin fiber

30 nm
Nucleosome

30-nm fiber

The 30-nm fiber, in turn forms looped domains, making up a 300-nm fiber
Protein scaffold

Loops

300 nm

Scaffold

Looped domains (300-nm fiber)

In a mitotic chromosome the looped domains themselves coil and fold forming
the characteristic metaphase chromosome
700 nm

1,400 nm

Metaphase chromosome

In interphase cells most chromatin is in the highly extended form called

euchromatin

VARIATION IN CHROMOSOME
STRUCTURE AND NUMBER

Chromosome Number in Different Species

In "higher organisms (diploids), members of same species typically have
identical numbers of chromosomes in each somatic cell. Diploid

chromosome number (2n). Nearly all chromosomes will exist in pairs

(identical wrt length and centromere placement) except the sex
chromosome Y. Members of pair are homologous chromosomes. Haploid
number (n) is the number of chromosome pairs.

Variation In Chromosome
Structure

Amount of genetic information in the chromosome

can change

Deficiencies/Deletions

Duplications

Single Chromosome Disorders

1. Deletion
2. Genetic material

1.Deletion

Genetic
material is
missing
2. Duplication
Genetic
material is
present twice

is present twice

3. Inversion

Deficiencies (aka Deletions)

A chromosomal deficiency occurs when a

chromosome breaks and a fragment is lost

Deficiencies

Phenotypic consequences of deficiency depends on

Size of the deletion

Functions of the genes deleted

Phenotypic effect of deletions usually detrimental

Cri-du-chat Syndrome

Duplications

A chromosomal duplication is usually caused by

abnormal events during recombination

Duplications

Phenotypic consequences of duplications correlated

to size & genes involved
Duplications tend to be less detrimental

Bar-Eye Phenotype in Drosophila

Phenotype: reduced number of ommatidia

Ultra-bar (or double-bar) is a trait in which flies have even

fewer facets than the bar homozygote
Both traits are X-linked and show intermediate dominance

Bar-eye Phenotype due to Duplication

Duplications and Gene Families

Majority of small duplications have no phenotypic effect

However, they provide raw material for evolutionary change

Lead to the formation of gene families

A gene family consists of two or more genes that are
similar to each other
derived from a common gene ancestor

Well-studied example is the globin gene family

Genes encode proteins that bind oxygen

Duplications Generate Gene Families

Genes derived
from a single
ancestral gene

Inversions

A segment of chromosome that is flipped relative to

that in the homologue

Centromere lies
within inverted
region

Centromere lies
outside inverted
region

Inversions
No loss of genetic information
Many inversions have no phenotypic consequences

Break point effect

Inversion break point is within regulatory or structural portion of a
gene

Position effect
Gene is repositioned in a way that alters its gene expression
separated from regulatory sequences, placed next to constitutive
heterochromatin

~ 2% of the human population carries karyotypically

detectable inversions

Inversion Heterozygotes

Individuals with one copy of a normal chromosome and one

copy of an inverted chromosome
Usually phenotypically normal

Have a high probability of producing gametes that are abnormal in

genetic content
Abnormality due to crossing-over within the inversion interval

During meiosis I, homologous chromosomes synapse with

each other

For the normal and inversion chromosome to synapse properly, an

inversion loop must form
If a cross-over occurs within the inversion loop, highly abnormal
chromosomes are produced

Crossing Over Within Inversion Interval

Generates Unequal Sets of Chromatids

Inversions Prevent Generation of Recombinant

Offspring Genotypes
Only parental chromosomes (nonrecombinants) will produce normal progeny
after fertilization

Translocations

When a segment of one chromosome becomes

attached to another

In reciprocal translocations two non-homologous

chromosomes exchange genetic material

Usually generate so-called balanced translocations

Usually without phenotypic consequences

Although can result in position effect

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Nonhomologous chromosomes

Fig. 8.13b(TE Art)

1 1

7 7

Crossover between
nonhomologous
chromosomes

Reciprocal
translocation
Nonhomologous crossover

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Fig. 8.13a(TE Art)

22

Environmental agent
2
causes 2 chromosomes
to break.

DNA repair enzymes

recognize broken ends
and connect them.

22

Reactive ends

Chromosomal breakage and DNA repair

In simple translocations the transfer of genetic

material occurs in only one direction

These are also called unbalanced translocations

Unbalanced translocations are associated with

phenotypic abnormalities or even lethality
Example: Familial Down Syndrome

In this condition, the majority of chromosome 21 is

attached to chromosome 14

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display

8-42

VARIATION IN
CHROMOSOME NUMBER