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Chromosome Structure and DNA

Essential Cell Biology (Second Edition) by Alberts et al.


Molecular Biology (Fourth Edition, Robert F. Weaver)
For Lab: Handouts will be supplied

See Chapter 5; Page 171-193


Office Hours

Monday- Thursdays 1:00 PM-2:00 PM


AB1 Building/1638 Bedford Ave
Room 403D
Focus is the Word
• What is the Color of the wall on you left?
a) White
b) Blue
c) Yellow
d) Red

• The color of the wall on the left is Pink. True of False


• What is the Color of the wall on your left?
Does not matter much whether the
question is MCQ, True or false
or short answer question
Objective

• Structure of Chromosome
• Structure of Nucleosome
• Composition of a Nucleosome
• Function of Histone
Each Chromosome can be Painted Differently, which helps
comparing normal to abnormal to pinpoint a particular disease

• This possible by using probes specific to each chromosome


that is labeled with a Unique Dye
The structure of Eukaryotic Chromosome
• Very long double-stranded DNA molecules are packaged into structures called chromosome.

Eukaryotic DNA is packaged into multiple


chromosomes
•In eukaryotes, the DNA in the nucleus is distributed among a set of chromosomes.
•Human genome - approximate 3.2 X 109 bases parceled into 24 chromosomes.
Chromosomal Banding Observed after Staining with Geimsa Stain

Red line indicates


Centromere
Banding Pattern of Human Chromosomes
• Red lines represents the position of centromere.
• A display of the full set of 46 human chromosomes is called human
karyotype.

• Chromosome contain long strings of genes.

• The most important function of chromosomes is to carry genes –the


functional unit of heredity.

• A gene is defined as a segment of DNA that contains instructions


for making a RNA or protein.

• Total number of genes ranges from 500 for a simple bacterium to


25000 for human.
Structural Organization of a Chromosome
Heterochromatin vs. Euchromatin
• The structure of chromatin varies along a single interphase chromosome.

• Heterochromatin and euchromatin are resented by different colors.

• Heterochromatin is deeply staining chromosomal material that


remains condensed in interphase, whereas euchromatin undergoes de-
condensation.
The DNA in Chromosome is Highly Condensed
Nucleosomes are the basic units of eukaryotic DNA structure.

Two classes of proteins are found to bind to DNA:


1) Histone: ~ 60 million molecules per cell
2) Nonhistone

http://www.youtube.com/watch?v=eYrQ0EhVCYA
The Structure of the Nucleosome Core
Particle
Each nucleosome core particle consists of : two molecules of each of histones H2A, H2B,
H3, and H4- and the double-stranded DNA- 147 nucleotide pairs long, that winds
around this histone octamer.
All four of the histones are relatively small with high proportion of
positively charged amino acids (arginine and lysine). The positive charge
help the histones to bind tightly to the negatively charged sugar-
phosphate backbone of DNA.

The numerous interaction explain in part why DNA of virtually of any


sequence can bind to histone core.

Each of the core histones also has a long N-terminal amino acid “tail”.

These histone tails are subject to several types covalent modification


that control many aspects of chromatin structure.
Regulation of Chromosome structure
A. ATP hydrolysis allow the chromatin remodeling complex to loosen the
nucleosomal DNA by pushing it along the histone core. This repositions (slides) the
nucleosome, exposing DNA to other DNA binding proteins.

B. Multiple rounds of nucleosome sliding can decondense chromatin.


DNA is the Blueprint
of Our Heredity

Nucleosomes
If Every Cell has 46 Chromosomes,
Then, They All Should Look Similar
and Perform Same Functions??

Neuron Macrophages Epithelial Cells


The “Tale” of Histone “Tails”
Two Nucleosomes are connected
by Histone H1
The Chemical Modification of Histone
Tails Serve as an Epigenetic Language to
Regulate Gene and Cellular Functions
Histone Acetyltransferase
(Lysine)
SET Domain (Lysine)

Ubiquitynase (Lysine)

Sumoylase (Lysine)

Kinase (Serine, Threonine


and Tyrosine)
Chemical Modifications Serve as a
Language during Gene Regulation

M Methylation
A

A Acetylation

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