DNA NUCLEOSOME

 Describe DNA location in Chromosomes

 Describe the Lowest Level of Chromosome
Organization
 Differentiate Chromosomes and Chromatin
 Describe how different levels of chromation
organization allows chromosome to be fitted
inside nucleus
 Differentiate heterochromatin (constitutive
and facultative) and euchromatin
• Chromosomes are discrete physical entities
that carry genes
• Autosomes occur in pairs in a given individual
(not the X or the Y chromosome)
• Sex chromosomes are identified as X and Y
• Females have two X chromosomes
• Males have one X and one Y chromosome
• The plans for making cells are coded in DNA
• DNA is organized into giant molecules called
chromosomes
• Each chromosome is a single DNA molecule
containing many genes
• Each gene gives the directions for making 1
protein
• In humans each chromosome has approximately
2000 genes (46,000 genes)
• Every gene has its place, or locus, on
a chromosome
• Genotype is the combination of
alleles found in an organism
• Phenotype is the visible expression of
the genotype
• Wild-type phenotype is the most
common or generally accepted
standard
• Mutant alleles are usually recessive
• The sequence of nucleotides
in a gene is a genetic code
that carries the information
for making an RNA
• A change in the sequence
of bases constitutes and
mutation, which can
change the sequence of
amino acids in the genes
polypeptide product
• Chromosomes have distinct
parts
• Centromeres:
• Hold duplicated chromosomes
together before they are
separated in mitosis
• Kinetochore proteins bind to
centromere and attach
chromosome to spindle in
mitosis
• Telomeres: ends of
chromosomes: important in
cell aging
• To make a new cell the old cell must duplicate
all its parts
• Duplication takes place in interphase
• DNA (chromosomes) duplicated in the S subphase
• Entire chromosome is duplicated at the same time
• The duplicated chromosome remains attached to the
original chromosome by its centromere
• The original chromosome and its duplicated partner
are called sister chromatids
 are made of chromatin, a complex of DNA
and associated protein.
 Before cell division, the chromatin
condenses, coiling and folding to make a
smaller package.
 Each duplicated chromosome consists of
two sister chromatids, which contain
identical copies of the chromosome’s DNA.
 As the chromosomes condense, the region
where the chromatids connect shrinks to a
narrow area, the centromere.
• Chromosomes – present as highly
extended nucleoprotein fibers called
chromatin
• Chromatin contains highly extended
nucleoprotein fibers (DNA, RNA,
associated protein)
• Human DNA: average human cell has
~6.4 billion bp of DNA divided among
46 chromosomes (2 meters long)
(estimated based on each base pair is
0.34nm in length)
• Nucleosomes - the lowest level of
chromosome organization
• DNA + associated proteins 
chromatin (nucleoprotein fibers)
• Histones are basic positively charged
proteins that are associated with
negatively charged DNA.
• Histones help package the DNA into
structural units called nucleosomes
• Roger Kornberg
(1974, Harvard)
– proposed that
DNA & histones
are organized
into repeating
subunits
(nucleosomes)
• This assembly
type increased
the DNA
packing ratio
to 40 fold
 • Each nucleosome
consists of a
nucleosome core
particle.
• Each particle consists
of eight core
histones (H2A, H2B,
H3, H4) assembled
into an octamer.
• The remaining histone
(H1) is called the
linker histone that
binds to the linker
DNA.
• Together the core
interact with 148 bp
• Ionic bonds (Non covalent bond) DNA and the linker
holds negatively charged with additional 20 bp
phosphate backbones of DNA and (Total 168 bp DNA)
positively charged histones
• Lowest structural level of DNA is 10
nm nucleosome core
• In EM, see “dots” 30 nm in diameter
(3X the nucleosome diameter;
chromatin cut in cross-section)
• Linker histones & core histones
implicated in higher-order chromatin
structure (fiber-like structure)
• Next stage of packaging - 30 nm fiber is
gathered into series of big, supercoiled
loops
• Typically, the DNA loops begin & end with AT-
rich sequences of variety of proteins
• Included among proteins is type II
topoisomerase that regulates the degree of
DNA supercoiling
• They untangle DNA of different loops when
they intertwine
• Loops are usually not visible, only revealed
during mitosis
 LEVELS OF
CHROMATIN
ORGANIZATION
Double helix DNA

Nucleosome core particle

Nucleosome filament

Chromatin fiber (Packed

nucleosome)

Supercoiled loops

Mitotic chromosome (Metaphase)

 Two types of chromatin after mitosis in
the diffuse interphase condition : and

euchromatin

heterochromatin
• The euchromatin is less intense and
is dispersed
 Euchromatin is a lightly packed form
of chromatin (DNA, RNA and protein) rich
in gene concentration
 Often under active transcription.
 Most active portion of the genome within the
cell nucleus - 92% of the human genome is
euchromatic, remainder is
called heterochromatin
BACK
• Heterochromatin (10%) remains condensed
throughout interphase and stains intensely,
indicating tighter packing
• Tightly packed form of DNA
the part of a chromosome that is
inactive in gene expression (no
transcriptional
activity) but may function in controlling
metabolic activities,
transcription, and cell division.
• Two types ;
 constitutive heterochromatin
 facultative heterochromatin
• Exist in compacted state most of the time
and permanently silenced.
• Constitutive heterochromatin is usually
repetitive (few genes) and forms structural
functions such as centromeres or telomeres
• If an active gene is accidentally moved
adjacently to a constitutive
heterochromatin; (as a result of
transposition and translocation) they will
become transcriptionally silenced –
position effect
• Is only silenced during certain phase of an
organism’s life, it can be activated!
• The case of the XX chromosome vs the XY
chromosome (Females have more genes?)
• Only one X chromosome is transcriptionally
active; the other one is a heterochromatic clump
called the Barr body
• X chromosome inactivation - Mary Lyon (British
geneticist, 1961) studied inheritance of coat color
in mice has made the following hypothesis:
• Heterochromatization of X chromosome in
female mammals occurs during embryo
gastrulation; inactivates genes on X
chromosome
• It is random in any given cell (could be
paternally or maternally derived X chromosome)
• Inactive X chromosome reactivated in germ
cells before meiosis, so both X chromosomes
become euchromatin & active during oogenesis.
• Therefore, all gametes get a euchromatic X
chromosome
• Paternal and maternal genes on X
chromosomes are different
• Adult females are genetic mosaics (with
different alleles functioning in different
cells)
• Reflected in the patchwork coloration
of the fur of some mammals (calico
cats)
• Pigmentation genes in humans are not
found on X chromosome so there are no
calico women.
Mosaicism in calico cats
• Mosaicism has been demonstrated in
women who are carriers for red-green color
blindness (patches of retinal cell with
defective color vision among patches of
normal vision)