So I am trying to brush up on my knowledge of HATs and HDACs.

I am reading the just the 1st paragraph of the background of this study

I remember learning that HATs turn things on on, and HDACs turn things off.

It says that sodium phenylbutyrate (PB), can epigenetically regulate gene expression by inhibiting histone deacetylase.

Does this mean that one of the effects this drug can have is turning the thing that turns things off to produce the effect of turning it back on? Similar to that of a double negative?



Yes, Sodium phenylbutyrate can upregulate the transcription of silenced genes by inhibiting the activity of Histone deacetylases (HDACs).
Histone acetylation performed by Histone acetyltransferases (HATs) helps in activation of genes, while deacetylation performed by HDACs is responsible for gene silencing. This makes HDACs a potent drug target to treat malignancies.

The inhibitors of HDAC regulate the chromatin structure which loosens the chromatin and hence effect the binding of transcription factors to DNA. This binding modulates the expression of genes playing role in cell cycle and apoptosis, thus effecting cell growth and differentiation. (Reference)

But this is not similar to double negative. Double negative is term used in embryogenesis, where a particular repressor gene is activated in specific regulatory state. (Reference)

  • $\begingroup$ Just for clarification - you are agreeing that PB acts as a negative feedback mechanism? (Not sure if that a better terminology than double negative?) Because when I used double negative I meant it in the sense that two negative processes could create a positive "constitutive on" for binding of TFs and hence turning gene expression? $\endgroup$ – user3665690 May 28 '20 at 21:06
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    $\begingroup$ yes.. you are right, but I think that term can't be used in this case. $\endgroup$ – Twinkle Sheen May 28 '20 at 21:09

Sort of. Histone deacetylases act on a particular region on the chromatin fiber to decrease or even silence the expression of the genes in such region. According to the study, PB has the capacity to inhibit the activity of histone deacetylases, which implies that the effect of PB, is to the make the cell less able to decrease the expression of certain genes, so one could crudely say that PB is turning off the thing that turns off the expression of certain genes, but this does not imply that it will turn the genes back on.


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