2. INTRODUCTION
• Eukaryotic chromosome consist of one linear, unbroken double
stranded DNA molecule.
• It is occur in nucleus. It consist of DNA and protein molecules.
This protein and DNA complex is known as chromatin.
• The total amount of DNA in eukaryotes is greater than bacterial
cells.
• It is highly compact structure.
• Eukaryotic chromosome structure refers to the levels of
packaging from the raw DNA molecules to
the chromosomal structures seen
during metaphase in mitosis or meiosis.
3.
4. CHROMATIN
• Chromatin is a substance within a chromosome consisting of
DNA and protein.
• The major proteins in chromatin are histones, which help in the
packaging of DNA in a compact form.
• During cell division, chromatin fibres condensed into
chromosome, which can be easily visible in anaphase.
• There are mainly two levels of chromatin organization:
• Euchromatin: DNA wraps around histone proteins,
forming nucleosomes complex and also called "beads on a string"
structure.
• Heterochromatin: Multiple histones wrap into a 30-
nanometer fibre consisting of nucleosome arrays in their most
compact form.
5.
6. HETEROCHROMATIN
• Heterochromatin is a tightly packed form of DNA or more
condensed.
• Because it is tightly packed, therefore it can not be transcribed by
RNA polymerase.
• Heterochromatin appears as small, darkly staining (dark band),
irregular particles scattered throughout the nucleus .
• Heterochromatin is usually localized to the periphery of
the nucleus.
• Heterochromatin mainly consists of genetically inactive satellite
sequences.
• Centromeres and telomeres are made up of heterochromatin.
• It is highly rich in AT sequence.
7. Heterochromatin is classified in to two groups.
1. Constitutive
2. Facultative
Constitutive heterochromatin: It remains permanently in
the heterochromatic stage. it does not revert to the
euchromatin stage.
Facultative heterochromatin: It can revert into
euchromatin that takes on the light staining.
8. • Euchromatin is a packed form of chromatin (DNA, RNA,
and protein) that is enriched in genes, and undergoes
active transcription.
• Euchromatin is the most active portion of the genome within
the cell nucleus.
• 92% of the human genome is euchromatic and highly rich in GC
content.
• The structure of euchromatin is an unfolded set of beads along a
string, whereas these beads represent nucleosomes.
• Euchromatin appears as light-colored bands after staining and
observed under an optical microscope.
• Euchromatin participates in the active transcription of DNA
to mRNA products. Not all euchromatin is necessarily
transcribed.
EUCHROMATIN
9. PROTEINS
• Chromatin consist of
protein apart from DNA.
• Mainly two type of protein
present with chromatin.
Histone protein
Non Histone protein
10. HISTONE
• Histones are highly basic
proteins found in eukaryotic cells.
• Its packaged with DNA
structural units called nucleosomes.
• Histones are abundant in lysine and arginine.
• Histone are the main protein components of chromatin, acting
as spools around which DNA winds, and allow to replication
and play a role in gene regulation.
• Without histones, the unwound DNA in chromosomes would be
very long (a length to width ratio of more than 10 million to 1
in human DNA).
• Histone protein consist of five units such as H1/H5, H2A, H2B,
H3, H4.
11. • H2A, H2B, H3 and H4 - Core
histones.
• H1/H5 - linker histones.
• The core histones all exist
as dimers, the resulting four
distinct dimers then come
together to form one
octameric nucleosome core,
(a solenoid (DNA)-like
particle).
• The linker histone H1 binds
the nucleosome at the entry
and exit sites of the DNA, thus
locking the DNA into place.
• It is responsible for eukaryotic
chromosomal organisation.
12. NON HISTONE
• Non histone proteins are acidic in nature.
• The non‐histone chromatin proteins are a heterogeneous group
of proteins.
• It act as a part of large multi subunit complexes, playing
important roles in regulating many processes such as
nucleosome remodeling, DNA replication, RNA synthesis and
processing, nuclear transport.
• Non-histone may interact with the nucleosomal structure of
chromatin and to produce specific regulatory effects.
• It is higher molecular weight component.
• Example: DNA polymerase
13. Core proteins are separated
from one another by linker
DNA.
Non histone protein
associated with the linker
DNA and few appear to bind
directly to core particles.
It helps in chromosal
packaging.
14. • Nucleosome model is a scientific model which explains the
organization of DNA and associated proteins in the
chromosome.
• It also explains the exact mechanism of the folding of the
DNA in the nucleus.
• The model was proposed by Kornberg in 1974 and is the
most accepted model of chromatin organization.
• It was confirmed and christened by P. Oudet et al., (1975).
• The packaging of DNA into nucleosomes shortens the fiber
length about sevenfold.
NUCLEOSOME MODEL
15. • A nucleosome is a section of DNA
that is wrapped around a core of
proteins.
• The nucleosome is the
fundamental subunit of
chromatin.
• Each nucleosome is composed of
a less than two turns of DNA
wrapped around a set of eight
proteins called histones, which
are known as a histone octamer.
• DNA and histones are packed
together to be nucleosome,
nucleosome form a pack which
are called chromatin, two
chromatin form a chromosome.
16. • Histones undergo posttranslational epigenetic
modifications that alter their interaction with DNA and
nuclear proteins.
• The H3 and H4 histones can be modified at several places.
• The core of the histones H2A and H2B can also be modified.
• Modifications of the histone
include methylation, acetylation, phosphorylation, and ADP-
ribosylation (Me: methyl, P: phosphate, Ac: acetyl).
• Histone modifications act in diverse biological processes such
as gene regulation, DNA repair, chromosome condensation
(mitosis) and spermatogenesis (meiosis).
HISTONE MODIFICATION
17. • Histones can be displaced
by chromatin
remodeling complexes,
thereby transcription and
translation process
continue by DNA
polymerases and other
enzymes.
• These processes are
reversible, so modified or
remodeled chromatin can
be returned to its compact
state after transcription
and/or replication are
complete.
18.
19. Histone Acetylation/Deacetylation
• Histone acetylation occur by the addition of an acetyl group from
acetyl coenzyme A.
• Enzymes used for the acetylation are called
histone acetyltransferases (HATs).
• The histone acetylation is involved in the regulation of many
cellular processes such as chromatin dynamics and transcription,
gene silencing, cell cycle progression, apoptosis, differentiation,
DNA replication, DNA repair etc.
• Histone deacetylaces (HDACs) catalyze the hydrolytic removal of
acetyl groups from histone lysine residues.
• Histone acetylation/deacetylation impacts chromatin structure
and gene expression.
• Acetylation of lysine residues leads to a transcriptionally active
chromatin structure (euchromatin) and deacetylation leads to an
inactive, condensed chromatin structure (heterochromatin).
20.
21. Histone Methylation/Demethylation
• Histone methylation is defined as the transfer of one, two, or
three methyl groups to lysine or arginine residues of histone
proteins by histone methyltransferases (HMTs).
• In the cell nucleus, when histone methylation occurs, specific
genes within the DNA complexed with the histone may be
activated or silenced.
• Arginine methylation of histones H3 and H4 promotes
transcriptional activation and is mediated by a protein arginine
methyltransferases (PRMTs).
• Histone demethylation is the removal of methyl groups in
modified histone proteins via histone demethylases.
• Histone methylation and demethylation are epigenetic
modifications that have the power to reduce or booster gene
expression, especially as a result of altering chromatin structure.
22. • Histone phosphorylation occur by the
addition of phosphate group and
dephosphorylation occur by removal of
phosphate group.
• Histones can be phosphorylated by protein
kinases and dephosphorylated
by phosphatases.
• Histone phosphorylation can occur on
serine, threonine and tyrosine residues.
• Histone phosphorylation plays main roles
in chromatin remodeling.
• Phosphorylation of H2A is an important
histone modification that plays a major
role in DNA damage response,
transcription regulation, mitosis and
apoptosis, this modification takes place on
serine residue.
Histone Phosphorylation