Detailed Structure of Chromatin

1. CHROMATIN
STRUCTURE
Mahrukh Shehzadi

2. Genetic Material in the Living Cells
 Cells contain a nucleus surrounded by a nuclear membrane in eukaryotic cells, and
a nuclear region in the prokaryotic cells.
 In a non-dividing cell the nucleus is filled with a thread-like material known as
"chromatin".
 Chromatin is made up of DNA and proteins (mainly histones and some non-histone
acidic proteins).

3. The Normal Human Chromosomes
 Normal human cells contain 23 pairs of homologous chromosomes:
i. 22 pairs of autosomes.
ii. 1 pair of specific chromosomes.
 Autosomes are the same in males and females
 Specific chromosomes are:
i. XX in females
ii. XY in males.
 Both X are homologous. Y is much smaller than X and has only a few genes.

4. Chromosomes
 One member of each chromosome pair is derived from each
parent.
 Somatic cells have diploid complement of chromosomes i.e. 46.
 Germ cells (Gametes: sperm and ova) have haploid complement
i.e 23.
 Individual chromosomes are recognized by
i. arm lengths ( p- short, q -long).
ii. centromere position (metacentric, sub-metacentric, acrocentric,
telocentric).

5. Composition of Chromosome
DNA
Histones
(Major proteins)
Non-histone
(Small amounts)
p
q
 The chromosomes themselves are macromolecular entities that must be
synthesized, packaged, protected, and properly distributed to daughter cells
at cell division.
 Significant segments of every chromosome are dedicated to these
functions.

6. Chromatin
 The complexes between eukaryotic DNA and proteins are
called chromatin.
 The major proteins of chromatin are the histones-small
proteins containing a high proportion of basic amino acids
(arginine and lysine) that facilitate binding to the
negatively charged DNA molecule.
 There are five major types of histones called
 H1,
 H2A
 H2B,
 H3,
 H4

7.  Nucleosome is the basic structural unit of chromatin.

8.  The nucleosome contains ~200 bp of DNA, organized by an octamer of small,
basic proteins into a bead-like structure.
 The protein components are called histones.
 Nucleosomal DNA is divided into the core DNA and linker DNA depending on its
susceptibility.
 Core DNA has an invariant length of 146 bp, and is relatively resistant to
digestion by nucleases (H2A, H2B, H3, H4).
 Linker DNA comprises the rest of the repeating unit. Its length varies from as
little as 8 bp to as much as 114 bp per nucleosome (H1)

9. Histone H1 - linker histone
 H1 linker histone – associated with linker DNA between
nucleosomes (about one H1 per nucleosome)
• Binds DNA at entry/exit
• stimulates folding 10 nm 30 nm fiber
• repressive effect on transcription – H1 binds weaker to
acetylated nucleosomes

11. NUCLEOSOMES

12.  Nucleosome (10 nm diameter):
• 8 histones in bead & 1 outside.
• Each bead: is surrounded by 146 bp DNA and there are 54-70
bp in the linker region.
• Space between beads is about 14 nm.

13. Levels of chromatin packing
 DNA and histone molecules form "beads on a string,"
consisting of nucleosomes in an extended configuration
 Each nucleosome has two molecules each of four types of
histone, around which the DNA wraps. The fifth histone,
called H1, can bind to DNA adjacent to a "bead."

15.  (b) With the help of histone H1, the string of
nucleosomes coils to form a chromatin fiber that
is 30 nm in diameter.
 (c) At the next level are looped domains of the
30-nm fiber. The loops are attached to a scaffold
of no histone proteins.
 (d) The chromatin folds further, resulting in the
maximally compacted chromosome seen at
metaphase.

16. Eukaryotic Chromosome Structure
 Eukaryotic DNA is packaged into chromatin.
 Chromatin structure is directly related to the control of
gene expression.
 Chromatin structure begins with the organization of the
DNA into nucleosomes.
 Nucleosomes may block RNA polymerase II from gaining
access to promoters.
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17. Two forms of chromatin
 Euchromatin – A lesser coiled
transcriptionally active region which can be
easily accessed by the RNA polymerases.
 Heterochromatin – A highly condensed
transcriptionally inactive region. The genes
in this region cannot be accessed by the
RNA polymerases for active transcription.
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18. Eukaryotic Chromosome Structure
 Methylation (the addition of –CH3) of DNA or histone proteins is associated
with the control of gene expression.
 Clusters of methylated cytosine nucleotides bind to a protein that prevents
activators from binding to DNA.
 Methylated histone proteins are associated with inactive regions of
chromatin.
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19. 8/19/2020 19
by HDACs and corepressors
leads to heterochromatin
formation

20. ↑Acetylation ----
↓ Condensation of DNA ----
↑ Transcription of genes in
that region
by HATs and coactivators
leads to euchromatin
formation
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21. Histone DNA interactions

22.  Histones contain a large proportion of the positively charged
(basic) amino acids, lyseine and arginine in their structure.
 DNA is negatively charged due to the phosphate groups on its
backbone. These result of these opposite charges is strong
attraction and therefore high binding affinity between histones
and DNA.
 Hydrogen bonding involving hydroxyl amino acids in the histone
peptide and the phosphodiester backbone of DNA and are also
important in further stabilizing the structure.