Question

What types of proteins are writers of the histone code and what is their general function?

Answer 1

Answer: Histone proteins are positively charged proteins which binds to the negatively charged DNA and give rise to highly condensed nucleosome or chromatin level structures to the DNA. Histone code is a hypothesis that states the functions of the DNA molecules are dependent to the associated histone protein molecules which are very much affected by the chemical modifications (methylation/acetylation/phosphorylation/ADP-ribosylation/ubiquitination/citrullination). The histones stabilize and destabilze the DNA molecules and also play important role in gene expressions. H1/H5, H2A, H2B, H3, and H4 are mojor families of histones amongst them H2A, H2B, H3 and H4 forms core Histones and H1/H5 formsHistone linkers. Various chemical modifications and their respective functions are described below:

Methylation: Histones are rich in lysine and arginine aminoacids. These amino acids have been reported to be modified by the methylation (addition of methyl group) and demethylation (removal of methyl group). For example,when methyl groups are added to lysines H3K4 and H3K36 by methyl tranferase enzymes it may lead to activation of the transcription mechanisms while demethylation of H3K4 by demethylases can silence the genomic region and inhibits it to be expressed.

Acetylation: When acetyl groups are added to histones by Acetylases then the bonding of DNA and histones get interrupted and DNA is free for gene expression while deacetylation of histones by deacetylases causes compact association of DNA and histone and DNA can not transcribe at this moment.

Phosphorylation: Histone phosphorylation and dephosphorylation generally occurs at the time of response by the cell in case of DNA damage. Phosphorylation to the serine aminoacid of the histones can initiate several signaling pathways in response to DNA damage.

ADP-ribosylation: Histones are excessively ADP-ribosylated by the ADP-ribosylases upon induced by DNA damage. it also send DNA repair signals to the cell.

Ubiquitination: H2A and H2B core proteins are mainly ubiquitinized by Ubiquitinases.  Ubiquitination to  H2A has been reporetd to repress the gene expression while Ubiquitination to  H2B can either activate or silence the gene expression.

Citrullination: In this process the arginine amino acid of the histone molecule gets converted to the citrulline and affect chromatin structure. It has been reported that the citrullination to H3 and H4 core histones are associated with inflammatory pathways and cell death.