2021/09/07

Epigenetic mechanisms and factors behind protein diversity

Instructions for protein production are not stored in DNA

The cell is able to use DNA very efficiently. By reading the same DNA sequence, a cell can produce thousands of different proteins without altering DNA. The best known DNA sequence from which a cell can produce up to 32,000 different proteins by alternative splicing is the Dscam sequence of a fruit fly. Such multifunctional utilization of DNA indicates not only the passive nature of DNA as a digital repository of information, but also that DNA doesn't provide instructions for protein production.

The accompanying study states quite unequivocally that alternative splicing, which is thus behind protein diversity, is driven by epigenetic mechanisms and factors.

https://www.cell.com/fulltext/S0092-8674(10)01378-4


Excerpts: "These insights suggest that epigenetic regulation determines not only what parts of the genome are expressed but also how they are spliced."

"A major recent discovery is that chromatin structure and epigenetic histone modifications act as key regulators of alternative splicing."


"Consistently, inhibition of histone deacetylation, DNA methylation, H3K9 methylation, and downregulation of heterochromatin protein 1α (HP1α) abolishes the siRNA-mediated effect on exon E33 splicing, suggesting a role of these modifications in alternative splicing regulation."

 



"These observations point to a role for epigenetic modifications in the regulation of alternative splicing, and this regulation may involve the modulation of RNA Pol II elongation rate."

"An advantage of such a histone-based alternative splicing regulatory system is that it would provide an epigenetic memory for splicing decisions that could be passed on during proliferation of a cell population and could be modified during differentiation without the requirement to establish a new set of alternative splicing rules at each step of differentiation. Obviously, an epigenetic alternative splicing memory would still require the proper expression of splicing factors, a process that itself may be controlled by epigenetic mechanisms. Regardless of mechanisms, it appears that epigenetic regulation is not limited to controlling what regions of the genome are expressed, but also how they are spliced."