Form Of Chromatin - Biochemistry

Form Of Chromatin - Biochemistry


Form Of Chromatin - Biochemistry Peter  

7 years ago

~10.1 mins read

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Forms of Chromatin

Heterochromatin
Think Hetero Chromatin, just like Hetero Sexual.
Heterosexuals are attracted to Opposite sex

So Hetero-Chromatin = Opposite of Chromatin:
Opposite of Chromatin because it does the opposite of Chromatin (Euchromatin).
i.e It does opposite of the function of Chromatin
As Chromatin’s function is to carry genetic information (DNA) and allow its expression.

Recall:
Chromatin = Condensed DNA and Histone
Condensed (DNA and Histone) to easily fit into the Nucleus
If Chromatin is Much More condensed = Heterochromatin = Much More letters (Hetero – 6 letters) = Much More Gene Suppression
If it’s Less condensed = Euchromatin = Less letters (EU -  2 letters) = Less gene Suppression.

Heterochromatin cannot be expressed:
Because Heterochromatin is Hypercondensed or extremely compressed, it would be very difficult to get to open it up for gene expression.
The DNA and Histone contained within it cannot be accessed. This is exactly opposite the function of chromatin.
Chromatin contains DNA and DNA is meant to be expressed.

Heterochromatin appears darker on EM (Electron Microscope).
So many chromatin hypercondensed/Extremely compressed together would look very dark (Opaque) under the electron microscope.
It appears dark (Opaque) because its compressed nature prevents light from passing through it. It is expected that when matter has been extremely compressed to make it fit into a space where it wouldn’t ordinarily fit into, it would also look a lot darker than matter that is less compressed because it can now fit in where only a few would have been able to fit.

Heterochromatin is transcriptionally inactive.
Transcription is the transfer of genetic information from DNA to RNA.
In heterochromatin, the DNA contained therein has been extremely compressed and cannot be easily relaxed/Uncoiled.
If DNA coil isn’t relaxed, its interior can’t be accessed and its genetic information cannot be read or transcribed into the RNA.
Hence, its remains transcriptionally inactive.

Heterochromatin is Sterically inaccessible.
Heterochromatin being sterically inaccessible refers to the fact that its hyper-compression leaves no room or free space through which it can be accessed from its outside.
As we discussed, Heterochromatin is Hyper-compressed, and so it would not be possible that we could find a vacuum or space or entrance opening through which even a very tiny molecule could access or enter into it.
If there was a little space to access the inside of heterochromatin from the outside, it would be said to be sterically accessible and we could easily go into it to uncoil it for transcription. 
Heterochromatin example = Barr bodies
Barr bodies (inactive X chromosomes) are heterochromatin.

Recall:
Barr bodies are inactive X chromosomes.
Usually present in the nuclei of females with two X chromosomes (XX) as a densely staining structure (Heterochromatin).

Females have two X chromosomes (XX).
One X would be active and the other inactive (Barr body).

Males have one X and one Y chromosome.
Both are active
If a male has more than one X chromosome, then he would definitely have a barr body(One hypercondensed X chromosome) .
Note that Inactivated X chromosome can only be present when there is more than one X chromosome.
e.g If a woman has only one X chromosome (Turner syndrome), none would be inactivated.
But if a person has 3 X chromosomes, one must be inactivated(Hypercondensed) and he would have 2 active X chromosomes.

Heterochromatin Mnemonics:
Pronounce Heterochromatin as HeteroCondensedTin (or HeteroComprestin) to remember that its Extremely condensed.
You can also think like this… HETERO has more letters and EU has fewer letters.
HETERO = Many Chromatin Condensed/Compressed together

EU = Few Chromatin Condensed/Compressed together

If you can remember that Heterochromatin is Heavily Condensed, you can easily remember every other thing about it (See summary)

Heterochromatin Summary:
Hetero-Chromatin = Opposite of Chromatin = Inactive Chromatin
Heterochromatin’s Highly compressed (Condensed) nature gives it the following characteristics:
Heterochromatin cannot be expressed
Heterochromatin appears darker on EM (Electron Microscope).
Heterochromatin is transcriptionally inactive.
Heterochromatin is Sterically inaccessible.
Heterochromatin example = Barr bodies

Euchromatin
Euchromatin = True Chromatin
Euchromatin is the opposite of Heterochromatin

Euchromatin is Less Condensed.
Its less condensed nature gives it all its characteristics (Opposite of Euchromatin)

It appears lighter on EM (Electron Microscope)
Because it is less compressed, it is less opaque and there are spaces between its molecules. Light could easily pass through these spaces and make it appear lighter under the electron microscope.

It is Transcriptionally active
Its less condensed/less compressed nature would allow tiny molecules like transcriptional enzymes to easily get in between its coils to uncoil/open it.

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Hence it would be easy for Genetic information to be transferred from the uncoiled DNA to RNA (Transcription).

It is Sterically accessible.
Euchromatin is less condensed (less compressed together) as we know.
There would be spaces between its molecules, these spaces make it easy for the inner parts of this molecule to be easily accessed from the outside. It can easily be opened to be transcribed or to take part in reactions.
(Sterically accessible: Just imagine two rooms A and B, A completely filled with stones while B with just a few stones in it – Logically, it would be easier to get into room B to open its windows than to get into room A to open its windows from inside.)

Euchromatin Mnemonics:
Pronounce Euchromatin as Leuchromatin (or Leuschromatin) to remember that its Less condensed. Leus = Less
 
You can also think like this… HETERO has more letters and EU has fewer letters.
HETERO = Many Chromatin Condensed/Compressed together
EU = Few Chromatin (Few) Condensed/Compressed together
If you can remember that Euchromatin is less Condensed, you can easily remember every other thing about it (See summary)

Euchromatin Summary:
EuChromatin = True Chromatin = Active Chromatin
Euchromatin’s Less compressed (Condensed) nature gives it the following characteristics:
Euchromatin is easily expressed
Euchromatin appears lighter on EM (Electron Microscope).
Euchromatin is transcriptionally active.
Euchromatin is Sterically accessible.

DNA methylation
Do not confuse with Chromatin Methylation or Hyper-Condensation.

 

Methylation
This is the addition of a methyl group to a molecule. The Methyl group is a very stable group because of its compact structure.

This means addition of a Methyl group to any molecule would stabilize or strengthen that molecule and make it difficult to open it up or access it to take part in reactions.

How the cell transfers Methyl group to molecules (Two Processes).

1. Methionine in the body is converted to S-Adenosyl Methionine (SAM) S-Adenosyl Methionine (SAM) is broken down to S-Adenosyl Homocysteine (SAH) and Methyl group.

         Tips to remember:

         M = SAM = SAH + M

i.e Methionine + S-Adenosine = S-Adenosyl Methionine = S-Adenosyl Homocysteine + Methyl

2. The enzyme Methyl-transferase (Just like its name it transfers Methyl groups to molecules) picks up these Methyl groups and transfers them to other molecules.

Two main reasons why DNA (DeoxyriboNucleic Acid) is methylated.
1)         To distinguish Old strand of DNA from New strand
2)         To repress (Prevent) Transcription of genes from DNA to RNA

Methylation: to distinguish Old strand of DNA from New strand
Template strand Cytosine and Adenine are methylated in DNA replication.
Remember with: Methylated CAT (“C” and “A” on Template)

Template strand is also called the Anti-codon.

“Anti-Codon (Anti-Genetic Codes)” = Lying Opposite the “Real Codon (Real Genetic code).

For definitions sake, we can say it complements the codon.  

Now we know methylation and we know Template strand and Coding strand.

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We also know that the coding strand is synthesized using the anti-coding strand as a template or foundation.

Consider that after the Coding strand has been completely synthesized from the Template strand, there would be two long complementary strands of DNA. Without methylation of one of the strands, the mismatch repair enzyme would be confused as it would not be sure which of the strand is the old (template) and which is the new (Coding strand)

The Mismatch repair enzymes are supposed to scan (go through) or check the newly synthesized strand for errors (i.e wrong placement/pairing/bonding of nucleotides between Template (Old) and Coding (New) strand).
If eventually there was an error in placement of new bases (Nucleotides) during production of coding strand. Mismatch repair enzymes would remove the wrong base and insert the correct one on the strand that is not methylated.
However, if no strand is methylated Mismatch repair enzymes could mistake the coding strand for the template strand and the Template for coding strand.
If this happens, it would remove the correct base from the template and replace it with a wrong base. It would also leave the coding strand with the wrong base.
This would result in gene mutation.
To prevent the event described above from occurring the Template strand Cytosine and Adenine must be methylated (Methylated CAT).
If the template strand is methylated, mismatch repair enzymes would not be able to change bases (Nucleotides) within it.
The Mismatch repair enzymes would be able to access only the new coding strand and as such any wrong base pairing between the Template and the coding strand would be corrected on the Coding strand leaving the stable Template strand intact.
Template strand methylation is very common in prokaryotes to ensure continuity and prevent mutations. 

Methylation: To repress (Prevent) Transcription of genes from DNA to RNA
DNA methylation at CpG islands represses(prevents) transcription.
Recall:
Methylation (Adding of methyl group) to a molecule stabilizes that molecule and prevents it from taking part in cellular processes or reactions.
Methylation at CpG islands would therefore make that part of the DNA extremely stable.

CpG Islands (Also CpG or CG sites):
CpG Islands are usually present at the starting point of genes in promoter regions.
Promoter regions act just like their names, they promote the transcription or transfer of genetic information from DNA to RNA.

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i.e We can say promoters are weaker points in DNA strand where enzymes that take part in transcription can easily bind and open up the DNA coding strand for transcription to occur.
If these CpG Islands present in the promoter regions are Methylated/Stabilized/Strengthened, you know that transcription enzymes cannot easily open up these strengthened regions and so transcription would not take place. 
The CpG sites or CG sites are regions of DNA where a cytosine nucleotide is followed by a guanine nucleotide in the linear sequence of bases along its 5' → 3' direction.
CpG is shorthand for 5'—C—phosphate—G—3' (C-G) that is, cytosine and guanine separated by only one phosphate;
Many genes in mammalian genomes have CpG islands associated with the start of the gene.
Recall:
Phosphate links any two nucleosides together in DNA.
Mnemonic:
Methylated Codons can’t Grow.
(While using the Mnemonics, bear in mind that Codons represent DNA coding strand, that would not be transcribed (Can’t Grow) when it is methylated)
(While using the Mnemonic Use the C in Codons and G in Grow to remember that its CpG or C-G Islands that is usually methylated)
 
Histone methylation
We know that Histones are proteins that are condensed together with DNA strand to form chromatin.
Since Histone is a part of Chromatin but not a part of DNA (DNA is the molecule that carries the genetic material) methylation of histone would not have a specific effect as methylation of a part of DNA.
Methylation of histones may have different effects on DNA transcription.
·  Methylation of histone can make them inaccessible and suppress transcription if the methylation occurs at point where the bond or interaction between the histone subunit and DNA is strong.
·  Methylation of histone subunits [Recall: 2 x (H2A, H2B, H3 and H4)] can also make DNA more accessible and hence increase transcription if Histone octamer is methylated at a point of weak interaction/bonding between the Histone and DNA strand.
It’s simple if Histone is methylated (Stabilized and prevented from undergoing further reactions) at a point where its interaction with DNA isn’t strong, DNA losses that point and so it would be easy to uncoil DNA from that point.

Methylation of Histone would also be reversible.
This is because Histone possesses the Enzyme Histone Demethylase
Lets break demethylase = de – methyl- ase
Lets say de-compress = remove compress
So we can can say de-methyl = remove methyl
Lets take Hydrol-ase = break down water
So we can say Methyl-ase = break down Methyl
Therefore De-methyl-ase = Remove Methyl and breaks it down.    
Usually reversibly represses DNA transcription, but can activate it in some cases depending on methylation location.
Histone Methylation Mostly Makes DNA Mute.

Histone acetylation

Recall:
Acetylation is the addition of acetyl group to a molecule.
Addition of acetyl group to any compound or molecule tends to cause expansion of the molecule. This is because the Acetyl group has an expanded structure. See diagram below

Introduction of an acetyl group into a Histone causes expansion of the histone structure.
The expansion of the histone structure in turn relaxes DNA coiling around it.
DNA is therefore easily transcribed.
Histone Acetylation makes DNA Active..

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