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“From gene to genomefrom histon to chromosome”

“Ghmkin hassan”حسن غمكين

Chromatin structure

Damascus university –pharmacy facultyDepartment of biochemistry

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Content

• Genome, how we see it ?• Nucleosomes• Beads on string• Higher-order chromatin structure: 30nm 300nm 700nm “chromosome”• Interphase chromatin.• Heterochromatin• Repetitive sequences.• Non coding RNA

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why?

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Genome, how we see it?

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DNA Molecules are Highly Condensed in Chromosomes

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1/10,000

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• Chromatin consists of:

• Histones • Nonhistone proteins.• RNA (small amount).

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Nucleosomes are a Basic Unit of chromosome Structure:

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Beads on string

• Nucleosome positing ,sliding

10nm

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Higher-order chromatin structure:

• Chromatin fiber: Interphase and mitotic chromatin

30 nm:

zigzag model

solenoidal structure

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solenoidal structure

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Fifth H1/H5

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Chromatin loops

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final level

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Interphase chromatin

“Chromosome Territories” “nucleolar organizing regions”

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Chromosome kissing

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Heterochromatin

• Inactive Chromatine heterochromatin : a highly condensed form

• Active Chromatin euchromatin.all the rest, which is less condensed

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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)

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Centromer & telomer

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How it form?

• "Histone Code” :• The covalent modification of core histone tails• Histone Variants

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Histone Variants

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Histon code

• A Complex of Code-reader and Code-writer proteins

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Repetitive sequencesthe 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

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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

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Middle Repetitive Sequences:VNTRs and STRs

• variable number tandem repeats (VNTRs). These repeatingDNA sequences may be 15 to 100 bp long and are found within andbetween genes. Many such clusters are dispersed throughout thegenome, 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 microsatellitesor short tandem repeats (STRs). Like VNTRs, they are dispersedthroughout the genome and vary among individuals in the numberof repeats present at any site. For example, in humans, the most commonmicrosatellite is the dinucleotide where n equals thenumber of repeats. Most commonly, n is between 5 and 50. Theseclusters have served as useful molecular markers for genome a

(CA)n

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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

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• 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.

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Noncoding RNAs and Chromatin Structure

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• Genome, how we see it ?• Nucleosomes• Beads on string• Higher-order chromatin structure: 30nm 300nm 700nm “chromosome”• Interphase chromatin.• Heterochromatin• Repetitive sequences.• Non coding RNA

summary

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