Histones

Histones

Q. 1

Histone acetylation causes?

 A >Increased Heterochromatin formation
 B >Increased Euchromatin formation
 C >Methylation of cystine
 D >DNA replication
Q. 1

Histone acetylation causes?

 A >Increased Heterochromatin formation
 B >Increased Euchromatin formation
 C >Methylation of cystine
 D >DNA replication
Ans. B

Explanation:

Increased Euchromatin formation [Ref: Lippincott’s Biochemistery 3/e p406, 420; Harper biochemistry 28/e p.315]

Histone acetylation promotes Euchromatin formation (transcriptionally active DNA).

Deacetylation and methylation promotes Heterochromatin formation (transcriptionally inactive DNA).

  • There are five classes of histones, designated HI, H2A, H2B, H3, and H4. These small proteins are positively charged at physiologic pH as a result of their high content of lysine and arginine. Because of their positive charge, they form ionic bonds with negatively charged DNA. Histones help in condensation of DNA into chromosomes.
  • Two molecules each of H2A, H2B, H3, and H4 form the structural core of the individual nucleosome “beads.” Around which a segment of the DNA double helix is wound nearly twice. (Histone HI, is not found in the nucleosome core, but instead binds to the linker DNA chain between the nucleosome beads.). Nucleosomes are further arranged into increasingly more complex structures that organize and condense the long DNA molecules into chromosomes.
  • These histone proteins can undergo reversible modifications at their N-terminal end (like acetylation, methylation or phosphorylation). These modifications help in regulation of gene expression.
  • Acetylation of the lysine residues at the N terminus of histone proteins removes positive charge on the lysine and thereby decreases the interaction of the histone with the negatively charged DNA. As a result, the condensed chromatin is transformed into a more relaxed structure allowing transcription factors to access specific regions on the DNA. Deacetylation restores the positive charge, causing stronger interactions between histones and DNA.
  • Thus histone acetylation enhances transcription while histone deacetylation represses transcription.
  • Relaxed, transcriptionally active DNA is referred to as euchromatin. More condensed, inactive DNA is referred to as heterochromatin.
  • Histone acetylation is catalyzed by histone acetyltransferases (HATS) and histone deacetylation is catalyzed by histone deacetylases (denoted by HDs or HDACs).
  • Another difference noted between transcriptionally active and inactive chromatin is the extent of methylation of cytosine bases in CG-rich regions (CG islands) of many genes. It has been observed that transcriptionally active genes are less methylated (hypomethylated) than their inactive counterparts.
  • Thus formation of euchromatin is promoted by acetylationand formation of heterochromatin is promoted by deacetylation and methylation. The action of methylation is indirect and has no effect upon charge.

Q. 2

Acetylation of histones results in which of the following modification?

 A

Increased Heterochromatin formation

 B

Increased mRNA production

 C

Activate Deacetylases

 D

Arginine Methylation

Q. 2

Acetylation of histones results in which of the following modification?

 A

Increased Heterochromatin formation

 B

Increased mRNA production

 C

Activate Deacetylases

 D

Arginine Methylation

Ans. B

Explanation:

Pretranscriptional control refers to the carefully controlled and selective unwinding of chromatin to facilitate gene expression.

It is known that modification of histones is functionally important in this process.

Enzymatic attachment of an acetyl group to certain amino acids in histones is critical – Acetylation of histones.

The acetylation of histones affects the charge interactions with DNA, resulting in unwinding of DNA at that specific location, and thereby facilitates subsequent steps required to generate nascent mRNA.

Conversely, deacetylation of histones can result in rewinding of chromatin and inhibition of gene expression. This modification of histones is carried out by a large family of enzymes termed histone acetyl transferases (HATs) and histone deacetylases (HDACs)

Why is this topic important and frequently asked?

1. Cardiovascular biology: E.g. Experimental studies in mice lacking specific HATs or HDACs can profoundly alter processes such as blood vessel development or cardiac hypertrophy.


Because acetylation and deacetylation are enzymatic processes, they are amenable to pharmacologic manipulation. Indeed, agents such as trichostatin A have been shown to ameliorate cardiac hypertrophy in rodents.

2. Chromatin modification: Acetylation is perhaps the most well-studied chromatin modification so far. However others such as lysine/arginine methylation, serine phosphorylation, and ubiquitination are also likely to be important areas from both a scientific and therapeutic perspective for the future.

Ref: Walsh R.A., Jain M.K., Proweller A. (2011). Chapter 6. Principles of Molecular Cardiology. In V. Fuster, R.A. Walsh, R.A. Harrington (Eds), Hurst’s The Heart, 13e.


Q. 3

Nucleoside is made up of:

1. Pyrimidine
2. Histone
3. Sugar
4. Purine
5. Phosphate

 A

1,2 & 3

 B

1,3 & 4

 C

1,3 & 5

 D

2,3 & 4

Q. 3

Nucleoside is made up of:

1. Pyrimidine
2. Histone
3. Sugar
4. Purine
5. Phosphate

 A

1,2 & 3

 B

1,3 & 4

 C

1,3 & 5

 D

2,3 & 4

Ans. B

Explanation:

“The nucleoside is composed of purine purine or pyrimidine base linked to either D-ribose (in RNA) or D-2- deoxyribose (in DNA)”

“The nuclear DNA is found bounded to basic proteins called histones”.
Nucleotides
  • Nucleotides are nucleoside +P
  • The Phosphodiester bond between the nucleotides is formed mainly between 3’OH group of sugar of one nucleotide to 3’OH group of sugar of another nucleotide.

 

Ref: Harper 27/e, Page 297; Chatterjee & shinde 7/e, Page 206-07.

Quiz In Between


Q. 4

True about Histone protein:

 A

Ribonucleoprotein

 B

Present inside the nucleus

 C

Acidic

 D

None

Q. 4

True about Histone protein:

 A

Ribonucleoprotein

 B

Present inside the nucleus

 C

Acidic

 D

None

Ans. B

Explanation:

B i.e. Present inside the nucleus;


Q. 5

Histone acetylation causes?

 A

Increased Heterochromatin formation

 B

Increased Euchromatin formation

 C

Methylation of cystine

 D

DNA replication

Q. 5

Histone acetylation causes?

 A

Increased Heterochromatin formation

 B

Increased Euchromatin formation

 C

Methylation of cystine

 D

DNA replication

Ans. B

Explanation:

B i.e. Increased Euchromatin formation


Q. 6

Histone has post – translational modification by all/except.

 A

Acylation

 B

Methylation

 C

Phosphorylation

 D

Glycosylation

Q. 6

Histone has post – translational modification by all/except.

 A

Acylation

 B

Methylation

 C

Phosphorylation

 D

Glycosylation

Ans. D

Explanation:

D i.e. Glycosylation

Quiz In Between



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