In laboratory studies, InsP6 activates the HDAC3 enzyme more effectively than other similar molecules, restoring more than half of its activity at a very low concentration (10 nM) in cells lacking...
Mechanism
Synthesis from 1 study
InsP6 is the only inositol phosphate that can lock into HDAC3 just right to turn it on, which shuts down genes that damage the gut lining. Other similar molecules are too weak to make this connection work.
Most probable mechanism
A specific molecule called InsP6 binds tightly to a protein called HDAC3, which then grabs onto another protein complex that turns off gene activity. This turns off genes that break down the protective lining of the gut, keeping it intact. Other similar molecules don't bind well enough to make this happen.
InsP6 binds directly to the catalytic domain of HDAC3 on chromatin
InsP6 binding induces a conformational change in HDAC3 that enables recruitment of the DAD domain of the NCoR1/2 corepressor complex
The HDAC3-DAD complex deacetylates histone H4 at lysine 16 at promoters of matrix metalloproteinase genes
Deacetylation of histone H4K16 represses transcription of matrix metalloproteinase genes
Reduced expression of matrix metalloproteinases prevents degradation of tight junction proteins
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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