Question

In contrast to histone acetylation, which always correlates with gene activation, histone methylation can lead to either transcriptional activation or repression. How do you suppose that the same modification - methylation - can mediate different biological outcomes? Explain what is meant when we say two DNA sequences are 'highly conserved'. Why are some sequences conserved and others aren't? In your own words, explain what is meant by "position effect". What is the molecular basis of this phenomenon?

Answer 1

Histone methylation is carried out by ‘histone methyltransfrases’. This activity decides the assembly of heterochromatin and also helps in maintain the boundaries between genes that are going to be actively transcribed. Activation or repression of transcription depends upon the amino acid being methylated and the presence of any other methyl groups or acetyl groups nearby to this histone. For instance, methylation of arginine and lysine residues leads to activation of transcription.

Highly conserved sequences are those that remain essentially unchanged over a period of evolution. It means that the gene is essential for survival and any changes in this gene is likely to be lethal. Examples include RNA components of ribosomes, certain TATA sequences, homeobox sequences which are conserved across all domains of life. These sequences can be either orthologous (identical sequences found across different species) or paralogous (identical sequences found within the same genome). Generally the sequences which code for amino acids essential for folding, structural stability and formation of binding site are usually conserved. Sequences which are variable or are not conserved may not be very essential for survival of the individual and the alternative forms also work well in these cases.

Position effect is when the expression of a gene is influenced by its interactive abilities with adjacent genes. If the spatial points of the genes are changed due to translocation, then its expression is also modified.