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“From gene to genome
from histon to chromosome”
“Ghmkin hassan”
‫غمكين‬‫حسن‬
Chromatin structure
1
Damascus university –pharmacy faculty
Department of biochemistry
Content
• Genome, how we see it ?
• Nucleosomes
• Beads on string
• Higher-order chromatin structure:
30nm
300nm
700nm “chromosome”
• Interphase chromatin.
• Heterochromatin
2
why?
3
Genome, how we see it ?
4
DNA Molecules are Highly Condensed in
Chromosomes
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1/10,000
.
7
• Chromatin consists of:
• Histones
• Nonhistone proteins.
• RNA (small amount).
8
Nucleosomes are a Basic Unit of chromosome Structure:
9
10
Beads on string
• Nucleosome positing ,sliding
10nm
11
Higher-order chromatin structure :
• Chromatin fiber:
Interphase and mitotic chromatin
30 nm:
 zigzag model
 solenoidal structure
12
solenoidal structure
13
Fifth H1/H5
14
Chromatin loops
15
16
17
final level
18
Interphase chromatin
“Chromosome Territories” “nucleolar organizing regions”
19
20
Chromosome kissing
21
Heterochromatin
• Inactive Chromatine
heterochromatin : a
highly condensed
form
• Active Chromatin
euchromatin.
all the rest, which is
less condensed
22
Constitutive heterochromatin:
always condensed and thus inactive
(found near centromers and telomers ).
Facultative heterochromatin:
at times condensed and at others
Uncondensed and actively transcribed
appearing as euchromatin
(X chromosome)
23
Centromer & telomer
24
25
How it form?
• "Histone Code” :
• The covalent modification of core histone tails
• Histone Variants
26
27
Histone Variants
28
Histon code
• A Complex of Code-reader and Code-writer proteins
29
the majority of repetitive sequences are nongenic
and, most serve no known function. We will explore
three main categories of repetitive sequences:
(1) heterochromatin found to be associated with
centromeres and making up telomeres;
(2) tandem repeats of both short and long DNA
sequences;
(3) transposable sequences that are interspersed
throughout the genome of eukaryotes
30
Centromeric DNA Sequences
what is Satellite DNA?
In humans, one of the most recognized satellite DNA sequences is the
alphoid family. Found mainly in the centromere regions, a 171- bp motif of
alphoid DNA is present in tandem head-to-tail repeating
arrays totaling up to 1 million base pairs. Embedded
somewhere in this repetitive DNA are more specific sequences
that are critical to centromere function. While such a motif is
present in other closely related primates, neither the sequence nor
the number of repeats of the human 171-bp sequence is conserved.
highly repetitive DNA, which constitutes about 5 percent of the
human genome
31
Middle Repetitive Sequences:
VNTRs and STRs
• variable number tandem repeats (VNTRs). These repeating
DNA sequences may be 15 to 100 bp long and are found within and
between genes. Many such clusters are dispersed throughout the
genome, and they are often referred to as minisatellites.
(ATTCCAGCCTTAACCG)n
• Another group of tandemly repeated sequences consists of di-,
tri-, tetra-, and pentanucleotides, also referred to as microsatellites
or short tandem repeats (STRs). Like VNTRs, they are dispersed
throughout the genome and vary among individuals in the number
of repeats present at any site. For example, in humans, the most common
microsatellite is the dinucleotide where n equals the
number of repeats. Most commonly, n is between 5 and 50. These
clusters have served as useful molecular markers for genome a
(CA)n
32
Repetitive Transposed Sequences:
SINEs and LINEs
• interspersed individually throughout the genome,
rather than being tandemly repeated. They can
be either short or long, and many have the added
distinction of being transposable sequences,
which are mobile and can potentially move to
different locations within the genome
33
• short interspersed elements, called SINEs, are less than 500
base pairs long and may be present 500,000 times or more in
the human genome. Alu family (the name is based on the
presence of DNA sequences recognized by the restriction
endonuclease AluI).
• long interspersed elements (LINEs) represents yet
another category of repetitive transposable DNA sequences.
LINEs are usually about 6 kb in length and in the human
genome are present 850,000 times. The most prominent
example in humans is the L1 family.
SINEs and LINEs represent a significant portion of human
DNA. SINEs constitute about 13 percent of the human genome,
whereas LINEs constitute up to 21 percent.Within both types of elements,
repeating sequences of DNA are present in combination
with unique sequences.
34
Noncoding RNAs and Chromatin Structure
35
36
• Genome, how we see it ?
• Nucleosomes
• Beads on string
• Higher-order chromatin structure:
30nm
300nm
700nm “chromosome”
• Interphase chromatin.
• Heterochromatin
37
summary
38

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Chromatin structure "DNA+CHROMOSOME"