Recently I've been studying the p53 tumor suppressor gene as a model for regulation of gene expression. It's amazing how many different post-translational modifications are known to regulate p53 activity, and how many different factors are involved in this regulation.

It is postulated that there are between 20,000 and 30,000 genes in the human genome. Is there an estimate for the percentage of these genes whose primary function is related to regulation of gene expression?

  • $\begingroup$ en.wikipedia.org/wiki/Transcription_factor $\endgroup$ – Amy Mar 2 '12 at 17:48
  • $\begingroup$ @Amy See my comment to Larry's answer. $\endgroup$ – Daniel Standage Mar 2 '12 at 19:53
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    $\begingroup$ I think you'll need to figure out a different way to phrase your question. "Gene expression" refers to transcription of open reading frames into mRNA. Post-translational protein modification is a separate cellular process and separate field of study with different terminology. $\endgroup$ – Amy Mar 2 '12 at 21:51
  • $\begingroup$ And I agree with @Shigeta - if you're getting into protein regulation and turnover, then you're pretty much just describing "life" $\endgroup$ – Amy Mar 2 '12 at 21:54
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    $\begingroup$ I'm saying that "gene expression" is separate from "protein expression." One refers to transcription and post-transcriptional modifications to RNA. The other refers to translation and post-translational modifications to proteins. And I strongly disagree with "protein is not fully expressed until it is functional" - there are plenty of genes that encode non-functional proteins. If they are translated, they are "expressed" $\endgroup$ – Amy Mar 2 '12 at 23:19

Okay, I'll take this out of the comments and put in an answer for all of us to work on.

To directly answer your question:

"Is there an estimate for the percentage of these genes whose primary function is related to regulation of gene expression?"

It depends on how you define "gene expression." And what cellular processes you want to include in that definition.

Larry's answer is the usual standard response, especially for people (such as me, ha) that have spent significant time studying transcription factors. About 1% of human genes have DNA binding domains and are thought to be directly involved in regulating the transcription of genes into mRNA - these are transcription factors (TFs). Closely related are cofactors, which regulate expression by binding to TFs or RNA polymerase machinery, but not directly to DNA.

Regulation of gene expression could also include modifications at the chromatin level - here you would include chromatin remodelers, histone acetylases, deacetylases, methylases and the histones themselves.

mRNA transcripts can also be regulated by miRNAs: post-transcriptional regulators that bind to complementary sequences on target mRNAs, which leads to translational repression or target degradation and gene silencing. So you would also include the proteins involved in this process, most notably the RNA-induced silencing complex, which includes Dicer.

There are also proteins involved in mRNA stabilization and turnover, which effects gene expression.

I'm not sure if anyone has added up all of the genes above to determine an overall percentage of the genome.

If you include in your definition of "gene regulation" post-transcriptional modification, folding chaperones, intra-cellular transport, extra-cellular and intra-cellular signaling, and so on - then Shigeta is right, you begin approaching 100%. In the most basic sense, life itself is gene regulation.

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Yes, look at FANTOM and their work. There are about 2000 transcription factors and co-factors in the human genome. These are proteins, of course. If you add a couple (or few?) thousand microRNAs and a few dozen anti-sense transcripts, although small in size, you inch that percentage upwards.

With some 70% of the human genome transcribed, by some estimates, one could argue that many of these non-coding RNAs (short, long, trans-spliced) act in some way to regulate the DNA to mRNA to protein process.

(I can send you those 2000 or so FANTOM TFs if you wish. Contact me by email.)

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  • $\begingroup$ Transcription factors are no doubt important in regulation, but my understanding was that TFs only regulate transcription. For many genes, post-translational modifications (phosphorylation by kinases, methylation by methyltransferases, etc) play an important role in regulating expression. I would like to include the genes encoding these factors in the estimate as well. $\endgroup$ – Daniel Standage Mar 2 '12 at 19:52
  • $\begingroup$ Just to be clear, by "regulation of gene expression" I meant to refer to anything that has to do with regulating transcription, regulating translation, regulating activity post-translation, and regulating degradation. Perhaps I should have worded that differently. $\endgroup$ – Daniel Standage Mar 2 '12 at 20:00
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    $\begingroup$ by these standards, the answer would be closer to 100% because any signalling protein would be involved, as well as the proteins that route signalling proteins around the various parts of the cell would be included. its hard to imagine a gene being deleted which would not affect the transcription of a gene under some conditions. Even metabolic enzymes would probably count as transcription is often regulated by the concentration of metabolites in the cell. $\endgroup$ – shigeta Mar 2 '12 at 20:08
  • $\begingroup$ @shigeta That is an excellent point. One reason I wrote the question in the first place is because I was beginning to wonder how such complex regulation schemes could be possible without the majority of genes in the genome being devoted primarily to regulation of other genes. And I understand that the question is complicated by the fact that proteins can have different functions in different contexts, which is why in the original question I used (perhaps naively) the words "primary function." $\endgroup$ – Daniel Standage Mar 2 '12 at 23:09
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    $\begingroup$ it seemed too difficult to put in an answer form. "everything is everything" is a common mindset you can slip into with cell biology and gene networks, but thanks for the suggestion. I have no real reference. its sort of a truism in the work. $\endgroup$ – shigeta Mar 5 '12 at 7:56

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