Epigenetic Therapy: New Modes of Regulating Gene Expression in Diseases! January 19
Contrary to the popular belief, our genes do Not code for any and everything! There are things beyond DNA sequences that can be inherited and result in specific phenotyes governing both normal and pathophysiological changes. Epigenetics refers to the study of heritable changes in gene expression that do not involve changes in DNA sequence. These changes may or may not cause change in final phenotype. To get a general idea about epigenetics, we must understand how DNA is arranged inside cells and how specific regions of DNA, called genes, are accessed by molecular motors for expression by a process called Transcription that form RNA which may further code for a polypeptide sequence by a process called translation.
Think of 2 long threads coiled around small glass beads over and over again. That exactly is how DNA is arranged inside the nucleus of the cells – threads refer to complimentary DNA strands and glass beads refer to histone proteins [we'll restrict ourselves to humans and other eukaryotic systems here, bacteria are little more weird systems!]. Eukaryotic DNA is closely associated with a set of proteins called histones to form a complex called nucleosome which coils upon itself to form highly condensed structure called chromatin – a meshed up yet highly ordered structure like this:
Now we need to access a particular area of this coiled up thread. Why? Because mere presence of genes do not do any good unless they are expressed in the form of final funtional proteins through mRNA. There are molecular machinaries for this purpose. They re-arrange DNA coiling, access specific sequences on DNA and express them as messengeer RNA which is taken out of nucleus and read by other machines to form proteins, like this:
Now, to access any particular area of this thread, we must loosen up the coils and depending upon our ability to access the desired area of the thread, specific genes shall either be expressed or remain silent. Cells have a lot of smart and tricky ways of doing this. They may modify either the thread (DNA itself) by methylation or the glass beads (histone proteins) to modulate their interaction by various chemical processes like methylation, acetylation and phosphorylation, as shown in the photograph below:
There are various enzymes that actively perform these processes, for instance, histone acetyltransferases (HATs) acetylate the lysine residues on histones and loosen up histone-DNA interactions to allow gene expression while histone deacetylases (HDACs) catalyze removal of acetyl groups from lysine residues and strengthen up histone-DNA interactions to prevent gene expression. So, by interfering with molecular mechanisms (by developing drugs against enzymes like HATs, HDACs, DNMTs etc.) that modulate these DNA-histone interactions to remodel Chromatin structure and allow/block expression of genes in various pathophysiological states, new modes of therapeutic interventions can be developed and that is essentially the crux of Epigenetic Therapy. The field of epigenetics is inspiring the discovery of newdrugs and is gaining importance in the arena of drug development.
Several potentially useful epigenetic drugs are undergoing preclinical and clinical trials while some others which are already hip have only recently been discovered for their epigenetic effects like in case of valproic acid which is used for seizures, bipolar disorder and cancer but was recently found to be an epigenetic drug as it acts as an effective HDAC inhibitor. Madam Pomfrey’s magical potions are about to be discovered and an exciting era in drug development lay ahead!
Tags: cancer, disease, Drug, Drug Development, drugs, Epigenetic Drugs, Epigenetic Therapy, gene, states
Brenda Horton Sep 26
I would like to know if this would change childrenthis research and how it affects transgender kids with transgender because it has been linked to epigeneome. I would like to know about