Does histone H3K9 de-acetylation stop gene expression?

In summary, acetylation of histones creates transcription activation rather than repression. More research is needed to figure out the role of histone acetylation in gene regulation.
  • #1
icakeov
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I've read in a few places that acetylation of histones creates transcription activation rather than repression (the common example being: H3K9).

What I am curious, with the absence of this acetylation (I'm guessing this would the process de-acetylation), do the genes that were previously acetylated actually stop expressing themselves?

If yes, would it be fair to say that this process is opposite from the classic methylation outcome, which represses by bonding, and activates by detaching.

I hope this made sense, still working on wrapping my head around some of these topics.
Any feedback really appreciated!

By the way, I think this paper touches on this and suggests that deacetylation directly creates chromosome condensation.
 
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There is certainly a lot of evidence showing that H3K9ac is commonly found at the promoters of actively transcribed genes, but it is still not completely clear whether this relationship is causal. For example, one could think of two explanations for why H3K9ac is at actively transcribed promoters: 1) H3K9ac is required for transcription or 2) transcription of the gene results in deposition of H3K9ac. Only if the first situation is true would one think that H3K9 deacetylation might stop gene expression.

There have been some studies that have tried to distinguish between the two scenarios by using CRISPR or other programmable DNA binding proteins to deliver enzymes that remove H3K9ac or other histone modifications in order to test their functions on gene expression. One such study suggests that deacetylation of H3K9 might reduce transcription (https://www.nature.com/articles/nature12466), though the mechanism is not completely clear. Similar studies suggest that H3K9 methylation is involved in gene silencing (e.g. https://www.nature.com/articles/nn.3871), so the effect could potentially be indirect; deacetylation itself may not directly affect transcription but deacetylation may be a necessary first step in the installation of H3K9 methylation which could be the more direct regulator of transcription. Of course, the opposite situation could be true as well (where H3K9me2 has no direct role in regulating transcription execpt through preventing H3K9ac) or some combination of the two.

AFAIK, biologists don't have a definitive answers to these questions and more research is required to study these issues (though I am not completely up to date on this field, so if anyone has references suggesting more conclusive answers to these questions, please let me know).
 
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Super helpful, thank you!
 

1. What is histone H3K9 de-acetylation?

Histone H3K9 de-acetylation is a process in which the acetyl group on the lysine residue at position 9 on histone H3 is removed. This results in a more compact and condensed chromatin structure, which can inhibit gene expression.

2. How does histone H3K9 de-acetylation affect gene expression?

Histone H3K9 de-acetylation can stop gene expression by causing the DNA to become more tightly packed, making it less accessible for transcription factors and other proteins that control gene expression. This can prevent the transcription of certain genes and therefore stop their expression.

3. What is the role of histone H3K9 de-acetylation in gene regulation?

Histone H3K9 de-acetylation is a key mechanism in gene regulation, as it can control whether certain genes are turned on or off. By changing the structure of the chromatin, histone H3K9 de-acetylation can regulate the accessibility of DNA to transcription factors, which in turn affects gene expression.

4. What factors can influence histone H3K9 de-acetylation?

Histone H3K9 de-acetylation can be influenced by various factors, such as enzymes called histone deacetylases (HDACs) that remove the acetyl group, as well as other proteins that can bind to histones and regulate their activity. Environmental factors, such as stress and diet, have also been shown to affect histone H3K9 de-acetylation.

5. Can histone H3K9 de-acetylation be reversed?

Yes, histone H3K9 de-acetylation can be reversed by enzymes called histone acetyltransferases (HATs) that add the acetyl group back onto the histone. This can result in a more open chromatin structure and can lead to increased gene expression.

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