Question

What is the role of histone methylation, acetylation, phosphorylation in chromatin remodeling?

Answer 1

Chromatins are the nucleoprotein complex of DNA found during interphase of dividing and G0 of nondividing cells. In metaphase, chromatin converted into more complex or condensed form termed as chromosome. Chromosome are normally shorter than DNA molecules as they are highly organized packed to fit in chromosome.DNA binded with proteins which help in their packaging are called Histone proteins. Histones are basic proteins which are replication dependent or independent.Normally histones are conserved proteins written as H1,H2A,H2B,H3 and H4.....in which H1,H2 are lysine rich whereas H3 and H4 are arginine rich.

Histone are responsible for first and most basic level of chromosome organisation called nucleosome. The nucleosome contains of histone octamer that consists of two copies of each H2A,H2B, H3 and H4.They are also known as core histone ,which are rich in lysine and arginine....means their positive charges can effectively neutralize the negatively charged backbone of DNA.

The modification of histone normally occur at the time of replication and transcription...which means either modification may increase or decrease the expression of gene.Methylation means simply addition of methyl group....which may mono,di,Tri...methyl and so on.

The lysine and arginine amino acids at the N terminus of Histone undergo methylation.Methylation of different part of the N terminus tail of H3 and H4 can cause both activation and repression of chromatin.... totally depends on the type of amino acid which get modified .For example ... methylation of lysine at 9 the position of H3 histone is associated with Gene silencing/ chromatin condensation whereas methylation of lysine at 4th position of H3 is associated with activation or transcriptional elongation ..So methylation can cause alteration in gene expression without changing the sequences of DNA.

Acetylation is termed as addition of acetyl group in histone proteins, after the enzymatic activity of Histone Acetyl transferase (HSTs).As we know the N terminus are called as histone tails where lysine and arginine were present.Acetyl group normally added to the Lysine amino acid and reduce the affinity of histone for DNA...because it removes the positive charge present on the histones.During acetylation nucleosome have possibility to form 30nm chromatin fibre structure .The histones which are acetylated normally form Euchromatin ...which means the condensed chromatin becomes relax and increase gene expression after increasing Transcription.

Phosphorylation is also known as transfer of phosphate group in histone protein.It also influences structure and have a significant impact on cellular activity. Gene expression is also controlled by post transcriptional histone phosphorylation.for example phosphorylation of Histone H3 and H1 is associated with the formation of metaphase chromosome.

So,in chromatin remodeling acetylation,methy methyl and phosporylation may activate or repress the process of Gene expression.