How gene expression is regulated? - Module 4 Reading / Watching

The DNA and histones that bind the DNA can undergo changes. These changes do not alter the nucleotide sequence and are not permanent, though they often persist through multiple rounds of cell division. These temporary changes can alter the chromosome structure as required. A gene can be turned on or off depending upon the location and modifications to the histone proteins and DNA. This type of gene regulation is called epigenetic regulation.
•Histone/nucleosome winding of the DNA molecule may change with the gene activity in a particular cell or tissue.
•When a gene needs to be transcribed but is unavailable because of histone proximity, moving the histone from the DNA strand can free the promoter and associated regulatory sequences so that the sequences are exposed and the  gene can be expressed.
•Conversely, if an active gene associated with a nucleosome must be turned off, then moving the DNA so that repressors can attach to the gene’s silencers can also be achieved by rewinding the DNA (in the next cell cycle) on the nucleosomes in a different way.
• Histone modification is a covalent post-translational modification (PTM) to histone proteins.
• N terminal tails of histone are modified  by

• methylation,

• phosphorylation,

• acetylation,

• ubiquitylation, and

• sumoylation. (small ubiquitin-related modifier (SUMO) family are conjugated to proteins to regulate such cellular processes as nuclear transport, transcription, chromosome segregation and DNA repair.)

• Histones modifications is  carried out by acetyltransferases and deacetylases, methyltransferases and demethylases.

• The PTMs made to histones can impact gene expression by altering chromatin structure or recruiting histone modifiers.

Histone -Lysine acetylation

Role of Histones in gene regulation

Histone Modifications

• Histone -Lysine acetylation is regulated by two enzymes:
• Histone Acetyltransferases (HATs)–use acetyl-CoA that is specifically recognized and bound by the Arg/Gln-X-X-Gly-X-Gly/Ala segment of HATs to transfer an acetyl group to the ε-amino groups on the N-terminal tails of histones .
• Histone Deacetylases (HDACs)–reverses the above modification by HATs
• Lysine acetylation causes a destabilization of the nucleosome and chromatin structure–effectively facilitating access to the DNA for various nuclear factors like the transcription complex.
• Hyperacetylated histones are regarded to be a hallmark of transcriptionally active chromatin.
• The work of HDACs increases the affinity between the nucleosome and the DNA, leading to a closed (heterochromatin-like) chromatin conformation that minimizes accessibility for the transcriptome.

Histone methylation

• This unique posttranslational modification is performed by a specific enzyme family known as the Protein Arginine N-Methyltransferases (PRMTs).
• Along with serine/threonine phosphorylation, and lysine methylation and acetylation, arginine methylation is an epigenetic histone modification that regulates gene expression as part of the histone code