At a concentration of 10 nM, inositol hexaphosphate enhances the enzymatic activity of HDAC3 in laboratory cell-free systems by promoting the interaction between the DAD domain of a corepressor...
Mechanism
Synthesis from 1 study
InsP6 acts like a molecular key that fits into HDAC3 and locks in its partner protein, turning on HDAC3’s ability to silence genes that damage the gut lining. This works even when the cell’s usual helper molecule is absent, making InsP6 the direct trigger for this protective process.
Most probable mechanism
A molecule called InsP6 binds directly to HDAC3, helping a specific part of its partner protein latch on tightly. This activates HDAC3 so it can remove acetyl groups from histones, which turns off genes that break down the protective lining of the gut. This happens even when another protein that usually helps make InsP6 is missing.
InsP6 binds directly to HDAC3 at a concentration of 10 nM, inducing a conformational change that enables interaction with the DAD domain of the NCoR1/2 corepressor complex.
The binding of the DAD domain to HDAC3 stabilizes the active conformation of the enzyme, enhancing its deacetylase activity.
Activated HDAC3 deacetylates histone H4 at lysine 16 at the promoters of matrix metalloproteinase genes.
Deacetylation of histone H4K16 represses transcription of matrix metalloproteinase genes, reducing protease production.
Reduced matrix metalloproteinase levels preserve tight junction proteins, maintaining epithelial barrier integrity.
Evidence from Studies
Supporting (1)
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Phytic acid (InsP6) activates HDAC3 epigenetic axis to maintain intestinal barrier function
Contradicting (0)
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