161 thoughts on “Twins and Epigenetics”

1. petrushka,

   endosymbiosis may not be a unique event.

   Yup, There are even triple-nested endosymbioses, and several organelles owe their origin to it.

2. Allan Miller:
   petrushka,
   Yup, There are even triple-nested endosymbioses, and several organelles owe their origin to it.

   The article suggests a case of irreducibility by erosion. By loss of everything not needed. Perhaps by replacement with an alternate structure.

3. …followed by couple of thousand words about the primacy of transcriptional activators over histone modifications…

   Only for that particular case. I’ve cited several cases where the transcriptional activation is subject to control of other mechanisms (like micro RNAs) in creation of pluripotentncy.

   In the case of the Queen Bee, transcription factors affecting histones are either subject to or bypassed by the effects of a substance that is not a transcription factor, namely the HDA10 in Royal Jelly.

   Furthermore there are other mechanisms that modify histones such as the PRC2 polycomb repression complex, etc. etc. Epigenetics is not all about transcription factors.

   Mukherjee’s highly misleading implication is that the “most important” thing that Yamanaka factors do is to modify histones.

   No, that’s not how I read the sentence! Mukherjee said,

   “Most important, epigenetic marks were erased and rewritten, resetting the landscape of active and inactive genes.”

   Which I interpret as the most important RESULT of Yamanaka’s quest, and that was what the Nobel comittee thought too. If you want to misread or give the most uncharitable reading of what someone writes, you most certainly are entitled to do that, but it doesn’t mean your rendering of what was written was the author’s intended meaning.

   As far as Henikoff, Ptachne arguing transcription factors are some sort of centerpiece or supreme in the hierarchy of mechanisms in epigenetics, that’s about as valuable as getting into the argument whether wheels or pistons are the most important parts of cars — not to mention I’ve identified mechanisms both in this thread and other threads that show where epigenetic marks are changed without the immediate participation of transcription factors. Transcription factors are actually impeded or facilitated by histone marks such as in chromatin remodelling.

   Here is another howler by Henikoff:

   , epigenetic processes analogous to those performed by the Yamanaka factors are performed by bacteria that entirely lack histones and DNA methylation.

   Yamanaka was dealing with cells that are part of a multicellular organism, bacteria are unicellular. Pluripotency is something bacteria don’t worry about since they are unicellular. Howler.

   Henikoff:

   Mukherjee seemed not to realize that transcription factors occupy the top of the hierarchy of epigenetic information, that this has been widely accepted in the broader chromatin field, and

   Oh Really?

   I just pointed out several instances where transcription factors are hardly mentioned in such a way for epigenetics!

   Histones and methylation marks are quite central to epigenetics and that is how the experiments of the Roadmap Epigenomics projects are organized.

   I cited one of the experimental techniques ChIP-Seq (Chromatin Immuno Precipitation Sequencing) for detection of histone modification (among other things such as protein/DNA binding). I provided a link to the ENCODE and modENCODE guidelines for conducting such experiments.

   Additionally, in one of the neglected diagrams listing the kinds of ENCODE experiments, one will see there is Whole Genome Bisulfite Sequencing (WGBS) which records the methyl marks on DNA.

   Henikoff:

   In no case that I recall is there an example of a change in gene expression that can be attributed to histone hyperacetylation to the exclusion of non-histone substrates, of which many have been identified.

   Histones modifications don’t happen by themselves, Mukherjee never suggested otherwise.

   However, a change in histone states do affect changes in gene expression — witness the carpenter ant and the effect of a histone modification on K27 on H3 — (see diagram below, look at the tail attached to H3, and you’ll see the K27ac enhancement iin the upper left center part of the diagram — there is also a star with the letters “Ac” for acetylation attached to the circle that says K27).

   That K27 bubble by the way can be changed by a cascade of events that involves the HOTAIR lncRNAs in conjunction with the PRC2 polycomb repression complex — which means makes Henikoff and Ptachne’s claims about transcription factors somehow being a the top of the epigenetic hierarchy is a dubious claim.

4. On correlation, causation and the unproven primacy of the histone code.

   The regulation of gene expression is fundamental to biology and is classically predicated on binding of transcription factor proteins to DNA. This view is challenged by large-scale studies correlating gene expression with posttranslational modifications of the histone proteins with which DNA is complexed in cells. Here, we show through a large-scale computational study that histone modifications can be predicted with remarkable accuracy from transcription factor-binding profiles, recapitulating known interactions between transcription factors and chromatin-modifying enzymes. Our results demonstrate that associations between gene expression and histone modifications do not necessarily imply a direct regulatory role for these modifications, but can be explained equally well as an indirect effect of interactions between transcription factors and chromatin-modifying enzymes.

5. stcordova: Only for that particular case. I’ve cited several cases where the transcriptional activation is subject to control of other mechanisms (like micro RNAs) in creation of pluripotentncy.

   Well, micro RNAs qualify as transcription factors, not HDACs. Nice own goal there, Sal.

   In the case of the Queen Bee, transcription factors affecting histones are either subject to or bypassed by the effects of a substance that is not a transcription factor, namely the HDA10 in Royal Jelly.

   Citation, please. Maybe it’s just the low opinion I have of your analytical chops, but for some strange reason I suspect that you have confused 10-HDA (the bee pheromone) with HDA-10 (the HDAC gene).
   Anyway, the concept that “transcription factors affecting histones” are regulated by things that aren’t TFs does NOTHING to detract from the primacy of TFs. Google ‘estrogen receptor’, kiddo. IFF you had an example of signal transduction that acted directly on HDACs/HATs, without affecting any TFs, then you would have a counter-example. I’m sure such exist somewhere. See if you can find one. [ETA: your Spannhoff et al. 2011 citation does not meet this hurdle]

   Which I interpret as the most important RESULT of Yamanaka’s quest, and that was what the Nobel comittee thought too.

   Curious, then, that the Nobel committee made no mention whatsoever of histone modifications, and only mentioned “epigenetics” as part of the historical landscape. They quite clearly focused on the real-world result of the EFFECT of introducing a set of TRANSCRIPTION FACTORS into mature cells.You are really shooting yourself in the foot here.

   If you want to misread or give the most uncharitable reading of what someone writes, you most certainly are entitled to do that, but it doesn’t mean your rendering of what was written was the author’s intended meaning.

   You might want to re-visit your reading of Henikoff in light of this sage advice.
   ROFL.

   As far as Henikoff, Ptachne arguing transcription factors are some sort of centerpiece or supreme in the hierarchy of mechanisms in epigenetics, that’s about as valuable as getting into the argument whether wheels or pistons are the most important parts of cars — not to mention I’ve identified mechanisms both in this thread and other threads that show where epigenetic marks are changed without the immediate participation of transcription factors.

   BTW, he spells his name “Ptashne” with an “s”. Attention to detail not your strong suit, I guess.
   But I do like your car analogy: likening TFs and HDACs to the wheels and pistons of a car.
   Respectively.
   [beat]
   Bacteria differentiate.
   [beat]
   When I first met her, my wife drove an RX-7
   [mic drop]

6. stcordova,

   Here is another howler by Henikoff:

   , epigenetic processes analogous to those performed by the Yamanaka factors are performed by bacteria that entirely lack histones and DNA methylation.

   Yamanaka was dealing with cells that are part of a multicellular organism, bacteria are unicellular. Pluripotency is something bacteria don’t worry about since they are unicellular. Howler.

   I think you’ve missed the point. Yamanaka factors are transcription factors, not histone modifications or DNA modifications. Analogous factors occur in organisms that completely lack histones and methylation. Unless you are saying that the sole function of Yamanaka factors and everything like them is to differentiate/reset differentiated cells, in which case there can be no prokaryotic analogue of such an activity? Still, I find it unlikely that Henikoff meant just differentiation when he referred to ‘analogous processes’. I think he meant regulation of gene activity.

7. Allan Miller,

   Still, I find it unlikely that Henikoff meant just differentiation when he referred to ‘analogous processes’. I think he meant regulation of gene activity.

   Just read Jock’s post, I should amend that to multicellular differentiation. And yes, not just any old regulation of gene activity, but that which affects morphology. Had a chuckle myself at the irony of complaint about ‘charitable reading’. It’s almost like we’re the same person.

8. Allan Miller,

   ISWYDT

   🙂

9. Goddamit

   Sal’s contortions are indeed amusing!

   So latest so far:

   Sal concedes that miRNAs are crucial to explain that aspect of gene regulation called epigenetics in the popular press, exactly along the very SAME lines that Mark Ptashne suggested.

   But, Sal does not comprehend that he has yet again contradicted himself.

   ITMT – we have known for a long time that Bacteria employ post-replicative DNA methylation and protein acetylation to regulate gene expression. Meaning epigenetics is remarkably unremarkable when one steps back to consider what we are all talking about.

10. Blah blah blah from TomMeuller who thinks transcription factors are made of RNAs. Tom doesn’t even understand the basics despite being spoon fed several times well known terminology:

    https://en.wikipedia.org/wiki/Transcription_factor

    In molecular biology and genetics, a transcription factor (sometimes called a sequence-specific DNA-binding factor) is a protein that binds to specific DNA sequences, thereby controlling the rate of transcription of genetic information from DNA to messenger RNA.[1][2

    Proteins are made of amino acids, not RNAs. Do you not even have elementary comprehensions of this stuff much less should you lecture me? LOL!

11. TomMueller needs elementary education in molecular biology.

    Ptachne talked about transcription factors that Yamanka ARTIFICIALLY enriched to induced pluripotency:

    The factors are:

    OCT-4 is a protein, not an RNA
    https://en.wikipedia.org/wiki/Oct-4

    Sox2 is a protein, not an RNA
    https://en.wikipedia.org/wiki/SOX2

    C-Myc is a protein, not an RNA
    http://www.sciencedirect.com/science/article/pii/S0014482799946864

    Klf4 is a protein, not an RNA
    http://www.uniprot.org/uniprot/O43474

    And additionally, Ptachne is not mentioned in the gold standard textbook on Epigenetics by Allis here:

    http://www.cshlpress.com/pdf/sample/2014/epigenetics2/EPIFM.pdf