species specific mouse transcription and the start of term

Term is about to start! I still can't believe that the holiday is almost over :( On the other hand, this holiday does seem to have gone on a while, memories of exams and lectures and learning seem so far away.

I will have to step away from being a Lab Rat for a while, and go back to being a Student. Lectures, reading, more reading, desperately understanding and (a new one for this year) Seminars. Seminars are where some other lab rat stands at the front of the room and talks about their lab ratting for a bit and then everyone else has to try to think of clever things to say about it. It's all great fun and sometimes you get free wine or food.

So as it's the start of term and I'm full of Good Intentions I went over to my departmental webpage to see if any of the abstracts for the seminars were up. It turns out that the first one is up. Here it is:

"Homologous sets of transcription factors direct conserved tissue-specific gene expression, yet transcription factor binding events diverge rapidly between closely related species. We used hepatocytes from an aneuploid mouse strain carrying human chromosome 21 to determine on a chromosomal scale whether interspecies differences in transcriptional regulation are primarily directed by human genetic sequence or mouse nuclear environment. Virtually all transcription factor binding locations, landmarks of transcription initiation, and the resulting gene expression observed in human hepatocytes were recapitulated across the entire human chromosome 21 in the mouse hepatocyte nucleus. Thus, in homologous tissues, genetic sequence is largely responsible for directing transcriptional programs; interspecies differences in epigenetic machinery, cellular environment, and transcription factors themselves play secondary roles."

I actually almost fainted when I read that. A few deep breaths later and I decided to come back to it and understand it. (Why can't scientists write what they mean?)

Translation (if you want to skip my waffle and get straight to a quick translation skip to the italic bit)

I have to admit that I had a bit of a clue to help with the translation, they gave me the guys webpage. A quick look confirmed that he works for cancer research UK, which helps because there are actually a limited number of things people in cancer research tend to work with (well, at the very least it confirms that he's not working with bacteria...)

So...the first sentence. Transcription factors are proteins that bind to the DNA and control its expression. Probably a term most biochemists should really know (heh). Homologous just means 'pretty much the same'. So their problem is that they've got transcription factors in very similar species doing wildly different things.

Hepatocytes are liver cells. Aneuploidy means 'an abnormal number of chromosomes'. So they basically just stuck human chromosome 21 (the smallest one! and, incidentally, the one that leads to Down syndrome) into mouse liver cells to see what they did. The idea being to find out whether the differences were caused by the actual nuclear material or the 'epigenetic' surroundings (epigenetic = stuff that isn't DNA)

Epigenetics is a relatively new and exciting concept incidentally. It's the idea that the actual nuclear environment has a large part to play in what gets expressed rather than just the DNA as much. Also it's an idea that really pisses off James Watson and anything that pisses off James Watson is fine by me.

So what happened? Were the alien chromosome 21's expressed like mouse chromosomes (showing epigenetic control) or exactly as they would be in humans (showing DNA control). The answer is in the third sentence, the chromosome 21's were expressed exactly the same as they were in humans. No epigenetics here :(

*these aren't the epigenetic controls you're looking for*

For those who just want a simple translation here it is, to the best of my ability:

Similar sets of transcription factors are involved in controlling the expression of mouse DNA. However the way they work is very different, even in closely related species. We placed the human chromosome 21 into mouse liver cells to see if they were expressed like mouse chromosomes (showing control from factors other than the DNA) or like human chromosomes (showing that all control is from the DNA). The expression of the chromosome 21 in the mouse liver cell nucleus was almost identical to the way it is expressed in humans. Therefore, in similar tissues, it is the genetic sequence that determines how the DNA is expressed, all other factors are secondary.

Now I've got to try and think of clever questions to ask about that. I might have a try at getting hold of the paper, then at the very least I can ask poncy questions about the techniques.