The amazingness of transcription factors.

[Kai]

Sitting here, preparing for a molecular biology exam tomorrow morning, I am struck with the utter beauty and simplicity that gives way to the emergence that is organized structure of tissues, organs, and all of that in relation to each other positionally, in animals especially. And the reason this is, the greatest reason that we are all beings constructed of great precision rather than just big blobs of randomized flesh and particles of different types of tissue all over,

Is Transcription Factors.

This /is/ a rant. Its a rant about how fucking awesome this shit is. And I'm going to try to explain it now, so you all can share in its complete awesomeness.


So, in higher eukaryotes (organism that have cell nuclei, like tripanosomes, earthworms and humans for example), unlike bacteria, have a whole lot of junk in their DNA. In fact, only about 30 % of our DNA sequence codes for proteins. The rest USED to be called "junk DNA", because it just all looked like random junk. Now, upstream of a coding sequence, there are all these little areas called enhancers. Enhancers can interact with proteins very specifically, and specifically, they interact with transcription factors.

Now, when you were conceived, your mother (or your mother's body really) kick started your development with a bunch of transcription factors. One she put at one end of the blobby embryo, another she put at the other end, and the back, and the belly. The diffusion of these transcription factors causes a gradient.

If you've ever seen a grid before, one of those number graphing grids, its pretty similar to how this all works. Go to one area of the grid and one transcription factor might be in high amounts (close to the butt end) but another might be in low amounts (far from the "head"), and two more are in equal amounts. You can see how this would sorta set the embryo out as a three dimentional grid with each little square having different amounts of transcription factors of different types.

Now, these original transcription factors bind to the enhancers of a specific gene in one particular area of the embryo, and for whatever reason, the interaction of the enhancers and the transcription factors and the DNA and the RNA Polymerase (the protein that transcribes the DNA to an RNA strand which can then be processed, sent out of the nucleus and made into Protein via ribosome), because this transfactor inhibits this one which enhances this one which inhibits two others which enhances this other one and feedsback and enhances the first one....

Because of this, the Polymerase binds on and takes off, makes the transcript. Now, turns out that THIS transcript codes for another transcription factor protein. See where I'm going with this?

The whole of the body is set out in a network grid of interacting transcriptions factors for which the whole of the body plan sets down on.

So, you have a gene for keratin, and you want your fingernails to be in the right place, but not for example on your forehead, or your cock.

The transcription factors at the end of your fingers during development are at just the right levels and types to interact just right with the enhancers on the gene that codes for keratin, and whoila! you've got fingernails in the right place!

So, from an initial few transcription factors from your mother, the embryo sets off a cascade of TFs flying up and down the body, compartmentalizing, segmenting, and all the right materials are getting made in all the right places.

So, what if you change one transcription factor sequence, or one enhancer sequence? Maybe it does nothing. Maybe you end up with brown eyes instead of blue, or blond instead of black, or you're missing your veriform appendix or your ears are a little lower. Or maybe its lethal, no survivors. Or MAYBE, something really novel, the idea that theres some latent gene in there somewhere that codes for the digestion of cellulose, and one transcription factor gets turned on and suddenly your stomach can breakdown wood pulp. THIS IS THE STUFF THAT EVOLUTION IS MADE OF. The genes for things like melanin, or keratin, or specific tissues are highly conserved, they don't differ much between species. But you change a TF here and an enhancer here and suddenly your organism of choice is looking completely different.

Most genes aren't expressed in a given tissue. Which ones are determines the structure and function. The transcription factors determine the location of the how and the why, starting from just a few at conception.

Kai,

Is in fucking AWE. You motherfuckers best bow to the universe in it's awesomeness.

[Kurt Christ]

This is why I love molecular biology. The processes have a breathtakingly beautiful logic and scale.

[Triple Zero]

That is fucking amazing indeed. I knew most of it already, cause when I was doing my machine learning research we teamed up with some biologists that were investigating "transcription factor binding sites" (such a mouth full, I think I will never forget the term though). Our meetings were pretty intense for me, I thought I knew most of the basic ideas of DNA RNA rhibosomes and how they make proteins from highschool biology, but it turns out there is a LOT more to it than just that

I agree with the Emergence part in this, I didnt know it was called Emergence back then, but I explained you about Kaufman networks once on IRC right? I learned that from the same prof that is leading that research group.

The thing about transcription factors causing DNA to be transcribed into new transcription factors causing DNA to be transcribed etc etc ... This is the actual "program" running the DNA, like an operating system. The part where it creates proteins that actually do something (like keratin) can be viewed as just a side-effect, like the output of a computer, when it prints characters to the screen, that is not what the computer really does it's all the switches that go behind the scenes that decide what it is that gets outputted, and the output itself is almost nearly an afterthought (although without it, the process would be kind of useless).

[Kai]

That is fucking amazing indeed. I knew most of it already, cause when I was doing my machine learning research we teamed up with some biologists that were investigating "transcription factor binding sites" (such a mouth full, I think I will never forget the term though). Our meetings were pretty intense for me, I thought I knew most of the basic ideas of DNA RNA rhibosomes and how they make proteins from highschool biology, but it turns out there is a LOT more to it than just that

I agree with the Emergence part in this, I didnt know it was called Emergence back then, but I explained you about Kaufman networks once on IRC right? I learned that from the same prof that is leading that research group.

The thing about transcription factors causing DNA to be transcribed into new transcription factors causing DNA to be transcribed etc etc ... This is the actual "program" running the DNA, like an operating system. The part where it creates proteins that actually do something (like keratin) can be viewed as just a side-effect, like the output of a computer, when it prints characters to the screen, that is not what the computer really does it's all the switches that go behind the scenes that decide what it is that gets outputted, and the output itself is almost nearly an afterthought (although without it, the process would be kind of useless).

I remember I asked my professor which came first, the organism or transfactors, and he started telling me about how the mother inserts the first transfactors into the embryo, and she got there by development and her mother's transfactors, and on and on and on.

This is a cascade thats been going on since literally the PreCambrian, over 600 million years ago at the advent of multicellular life forms.

And yeah, I remember, cause I had just read Reinventing the Sacred and Kauffman was going on and on about his boolean networks.