Download Chromosomes and Histone protein

Chromosomes
Bashdar Mahmud Hussen
M.Sc. Biotechnology
Hawler Medical University, Iraq
[email protected]
[email protected]
History of Chromosome
Karl Nagali (1842)
E. Russow (1872) first description
A. Schneider (1873) chromosomes & cell division
Strasburger (1875)
Walter Flemming (1877) chromatin
W. Roux ( 1883) chromosome & inheritance
Male vs Female
• MALE
• Usually the Y
chromosome.
• Y is usually smaller
• Male genotype = XY
• FEMALE
• Usually the X
chromosome.
• Larger than the Y
• Female genotype XX
Except Birds
Male = XX
Female = XY
Number of chromosomes
• Normally, all the individuals of a species have the
same number of chromosomes.
• Presence of a whole sets of chromosomes is called
euploidy.
• It includes haploids, diploids, triploids, tetraploids
Polyploidy.
• Gametes normally contain only one set of
chromosome – this number is called Haploid
Somatic cells usually contain two sets of chromosome
2n : Diploid
Tijo and Levan
Chromosome Size
• In contrast to other cell organelles, the size of
chromosomes shows variation depending on the stages
of cell division.
Interphase: chromosome are longest & thinnest
Prophase: there is a progressive decrease in their length &
increase in thickness
Anaphase: chromosomes are smallest.
Metaphase: Chromosomes are the most easily observed
and studied during metaphase when they are very thick.
Therefore, chromosomes measurements are generally taken
during mitotic metaphase.
CHROMOSOME MORPHOLOGY
(A–T)
Telomeres
Chromosome Structure
Centromere
Short arm
Telomere
Centromere
Metacentric
Chromosome
Long
arm
Submetacentric
Chromosome
Acrocentric
Telocentric
Chromosome Chromosome
Centromeres and Telomeres
• Centromeres and telomeres are two essential features
of all eukaryotic chromosomes.
• Each provide a unique function i.e., absolutely
necessary for the stability of the chromosome.
• Centromeres are required for the segregation of the
centromere during meiosis and mitosis.
• Teleomeres provide terminal stability to the
chromosome and ensure its survival
Material of the chromosomes
The nucleoplasm contains many thread like coiled and
elongated structure which take basic stain are called
chromatin.
Chromatin consists of :
1. (1:1)
2. (1:0.6)
3. (1:0.1)
Euchromatin
 Portions of chromosomes that stain lightly are
only partially condensed, this chromatin is called
Euchromatin.
 It represents most of the chromatin that separate
after mitosis.
 It contains structural genes which replicate and
transcribe during G & S1 phase of interphase.
Heterochromatin
In the dark staining regions, the chromatin remains
in the condensed state and is called heterochromatin
It is characterized by high content of repititive DNA
sequences.
It is thought that in the heterochromatin, DNA is
tightly packed in the form 30 nm fiber.
• Heterochromatin has been further classified into two groups:
(i) Constitutive
(ii) Facultative.
Constitutive heterochromatin remains permanently in the
heterochromatic stage, i.e., it does not revert to the euchromatic
stage.
Facultative heterochromatin such type of heterochromatin is
not permanently maintained in the condensed state; instead it
undergoes periodic dispersal & during this time is transcription
ally active. Ex. X-chromosome in the mammalian female.
Euchromatin (E) vs Heterochromatin (H)
Fig. 11
H
E
DNase
Being more condensed (tightly packed),
heterochromatin is resistant to DNase digestion.
Chromosomes in eukaryotes
• Found in the nucleus
• Condensed and visible during cell division
• At the beginning of mitosis they can be seen to consist of
two threads (sister chromatids) joined by a centromere
• The sister chromatids are identical copies
• During mitosis the sister chromatids separate and are
placed into two nuclei
Bacterial Chromosome
• Single, circular DNA molecule located in the
nucleoid region of cell
Chromosomes in eukaryotes and
prokaryotes are different
PROKARYOTES
EUKARYOTES
single chromosome plus plasmids
many chromosomes
circular chromosome
linear chromosomes
made only of DNA
made of chromatin, a
nucleoprotein (DNA coiled
around histone proteins)
found in cytoplasm
found in a nucleus
copies its chromosome and divides copies chromosomes, then the
immediately afterwards
cell grows, then goes through
mitosis to organise
chromosomes in two equal
groups
Human genome
•
•
•
•
Human genome (in diploid cells) = 6 x 109 bp
6 x 109 bp X 0.34 nm/bp = 2.04 x 109 nm = 2 m/cell
Very thin (2.0 nm), extremely fragile
Diameter of nucleus = 5-10 mm
• Most human cells are diploid and each cell contains a
total of 2 m of DNA
• 2 X 1014 cells = 2 X 1014 meter
• Total DNA length of 2 X 1011 km
Compare this with the circumference of the earth
(4 X 104 km) or (1.5 X 108 km) the distance between
the earth and the sun.
DNA must be packaged to protect it, but must still be
accessible to allow gene expression and cellular
responsiveness, How ?????
The major histone proteins
Histone Mol. Wt
H1
H2A
H2B
H3
H4
22,500
13,960
13,774
15,273
11,236
No. of
Amino acid
244
129
125
135
102
Percentage
Lys + Arg
30.8
20.2
22.4
22.9
24.5
The DNA double helix is bound to proteins called histones. The
histones have positively charged (basic) amino acids to bind the
negatively charged (acidic) DNA. Here is an SDS gel of histone
proteins, separated by size
In addition, chromatin contains an approximately
equal mass of a wide variety of non-histone
chromosomal proteins.
There are more than a thousand different types of
these proteins, which are involved in a range of
activities, including DNA replication and gene
expression.
The DNA of prokaryotes is similarly associated with
proteins, some of which presumably function as
histones do, packing the DNA within the bacterial cell.
1st level
2nd level
3rd level
Core DNA
Packaging of the DNA in to chromosome has
several important functions
1. This compact form fits to inside the cell.
2. It protect DNA from damage.
3. Only chromosomes can transmit efficiently to
both daughter cells.
4. Chromosome give the organization to each
DNA, this organization facilitates gene
expression.
Nucleosome core particle
individual nucleosomes = “beads on a string”
• Detailed analysis of these nucleosome core particles
has shown that they contain 146 base pairs of DNA
wrapped 1.75 times around a histone core consisting
of two molecules each of H2A, H2B, H3, and H4 (the
core histones).
The Assembly of the Core Histones
Notice the long tails of the octamer
The bending of DNA in a nucleosome
1. Flexibility of DNAs: A-T riched minor groove inside and G-C
riched groove outside
2. DNA bound protein can also help
30-nm fiber
Flexible linker, DNA binding proteins
Structural modulators: H1 histone, ATP-driven Chromatin
remodeling machine, covalent modification of histone tails
Function & location of Histone H1
It is essential for the second level of chromatin
organization.
The function of
Histone tails
Chromatin Remodeling
Cyclic Diagram for nucleosome formation and disruption
ATP
Less tightly bound
Covalent Modification
of core histone tails
Acetylation of lysines
Mythylation of lysines
Phosphorylation of
serines
Histone acetyl
transferase (HAT)
Histone deacetylase
(HDAC)