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Are all genes capable of being switched on or off or only some genes? Are there some genes that permanently do not have the functionality that enables them to be switched on or off?

Everything I have found in response to this question seems to assume that ALL genes are capable of being switched on or off.

When I have searched for the answer to this question all I find are explanations about how things like epigenetics, gene regulation and expression work. I understand at the basic level how these things work and that there are different ways by which they are accomplished.

I realize the answer may be "as far as we know" or "we don't know" or "it's complicated" and that's fine and definitely understandable.

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    $\begingroup$ Welcome to SE Biology. This is a question and answer site where we hope the Q&A will be of general benefit. For that reason we try to ensure that questions are unambiguous, editing if necessary. Hence two requests for clarification. 1. Are you taking about bacterial or eukaryotic cells? 2. By “switching off” do you mean specifically prevent transcription of a gene, excluding general effects of starvation of metabolites? $\endgroup$
    – David
    May 15 at 16:31
  • $\begingroup$ Eukaryotic. I expect "prevent transcription" is the appropriate clarification but preventing something is different than lacking the functionality for something. With regards to my question either would have the same effective result - a gene where regulation is not possible. $\endgroup$
    – NetCentric
    May 15 at 18:39

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I cannot think of a mechanism that would entirely prevent a gene from being regulated. For example, consider mechanisms like histone modification: there is very little about the sequence of a single underlying gene that can itself cause or prevent histone modification, yet those changes regulate the expression of associated genes. However, you can really only provide evidence in science for things that happen; providing evidence that things do not happen is often questionable. If you have some example gene and you'd like to say "this gene is not regulated", the best you can ever get to is "I haven't yet found a circumstance in which this gene is regulated by any manipulation I know of".

In practice, there are some genes that are not typically "switched on/off" and always expressed at fairly constant rates, we call these housekeeping genes. For many of these, the consequence of 'switching them off' would be death of the cell. However, I would not consider that these genes are "not capable" of being regulated, rather, I would say that they are specifically regulated to be always active, and that there is very strong evolutionary pressure for this to occur. To show that I mean by this, consider some quoted lines from Wikipedia:

The housekeeping gene expression levels are fine-tuned to meet the metabolic requirements in various tissues. Biochemical studies on transcription initiation of the housekeeping gene promoters have been difficult, partly due to the less-characterized promoter motifs and transcription initiation process.

Little is known about how the dispersed transcription initiation of housekeeping gene is established. There are transcription factors that are specifically enriched on and regulate housekeeping gene promoters.[12][13] Furthermore, housekeeping promoters are regulated by housekeeping enhancers but not developmentally regulated enhancers.[14]

In summary, steady activity is carefully controlled, and difficult to study. Comparatively, if a gene has very different expression in different environments, you can follow an iterative process to look at cells in each environment and see what is different: if you find another protein is phosphorylated or otherwise modified, or has also changed expression, you might be looking at a transcription factor involved in your gene of interest. On the other hand, if something never changes, where do you start? Trickier problem for an experimentalist.

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  • $\begingroup$ Thank you very much for your comprehensive answer. I do appreciate you taking the time to provide links, quotes and your thoughts. $\endgroup$
    – NetCentric
    May 16 at 17:19

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