Epigenetics refers to modifications to the DNA, as well as to the histone proteins that DNA wraps around to form chromatin. Here's a decent review that goes over some of these modificatons. Some have requested a simplified or layman's description of how apabetalone works. Below, I provide some background that hopefully simplifies the understanding of apabetalone, bromodomains, chromatin and how they related to gene transcription. I think a few potential analogies for how apabetalone works are: Dimmer Switch. Chill Pill. Smokescreen. Blurred Bromodomain Vision. Acetyl-lysine Illiteracy.

The central dogma is: DNA --> RNA --> protein. DNA is transcribed to messenger RNA (mRNA), which is then translated to the functional protein. Epigenetics deals with the first step: DNA --> RNA, in which the transcriptional machinery is recruited to the DNA, reads the DNA and synthesizes a complimentary mRNA strand. However, DNA is not a simple, linear 2-dimensional molecule. It is wrapped around histone proteins to package and order DNA into chromatin. Epigenetic modifications influence whether the chromatin is tightly packed or loosely packed. More tightly packed chromatin is less accessible to the transcriptional machinery, while more loosely packed chromatin is more accessible to the transcriptional machinery. Histone acetylation is one of the forms of histone modifications that influences chromatin structure. Histone acetylation will loosen, or open, the chromatin structure to turn on gene transcription. Regions of chromatin without much histone acetylation will be tighter/compact, or closed, which turns off gene transcription. So histones with adundant acetylation --> open chromatin --> active gene transcription; histones with minimal acetylation --> closed chromatin --> inactive gene transcription. 

To borrow from this review "Bromodomains are structural motifs binding to acetylated lysines. BETs bind to specific acetylated lysines on histone tails, and thereby facilitate the assembly of the transcriptional machinery." Histone acetylation leads to open/active chromatin. The BET bromodomains "read" the DNA by recognizing the histone acetylated lysines that are prevalent on open/active chromatin regions, and facilitate gene transcription by helping to assemble/recruit the necessary transcriptional machinery. Apabetalone, and other BET bromodomain inhibitors, interfere with the ability of the bromodomains to bind to the acetylated lysines and therefore interfere with the transcription of genes that reside in the open/active chromatin.

In certain disease states, chromatin structure is altered by changes in the histone lysine acetylation pattern that results in the loosening of certain chromatin regions and increased expression of genes residing in that chromatin region. This leads to a certain gene expression signature for this disease. Normally, BET bromodomain proteins would promote gene transcription by recognizing these acetylated lysines on histones and helping to assemble/recruit transcriptional machinery. This is where BET inhibitors have their effect. Genes that would be highly expressed/active are now expressed at lower levels/inactive.

Growacet your "switch" analogy is OK, but you have it the wrong way. Apabetaone leads to switching off of genes that would otherwise be switched on. Furthermore, apabetalone binds to the bromodomain of the BET protein, not to the DNA, to prevent bromodomain binding to acetylated lysines. I prefer a dimmer switch analogy, since it is dialing things down gene expression, but not turning gene expression completely off. Returning gene expression to the "basal" level as Tada wrote. However, apabetalone isn't really waking up lazy genes to turn them back on. Instead, BET inhibition is more related to turning off, or dimming, overactive genes. 

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