FL Thoughts Out Loud

It’s often the case that I get an idea but don’t have the time to write up a decent blog to spell it out.  As a result, some ideas come and go.  So I will start a new tag entitled, FLE ruminations.  Here I will jot down ideas for possible future reference and/or expansion.  We’ll kick it off with some stuff that is in the process of connecting genomic shape to front-loading:

Now that’s a Horror Movie

He’s After Ya

Cute Bunny

Alu Mania

I’ve been talking about Alu elements for weeks now, so I was going to try to change the topic.  But alas, I can’t stop myself.  Here is some more Alu Fun for those similarly intrigued by the manner in which these nifty reformatting devices can facilitate evolution.

First, here is a decent video that outlines the basics of Alu retrotansposition.

Second, remember how it has become clear that the genome has a three-dimensional architecture?

Nudging the nudge

We have seen that the Alu element is poised to generate binding sites for multiple transcription factors involved in development.  Even more interesting is the manner in which the process of cytosine deamination can easily create several of these transcription factor binding sites.  It’s as if we have two nudges, working together, to facilitate the evolution of primates.

Yet there is more to the story.  Recall that the cytosine deamination events occur at CpG sites.This is simply where a cytosine (C) is followed by a guanine (G).  Why is this?

It just doesn’t stop!

The title of yet another paper speaks for itself: Alu elements contain many binding sites for transcription factors and may play a role in regulation of developmental processes (Paz Polak and Eytan Domany. BMC Genomics. 2006; 7: 133).

Let’s look at the abstract.

This research suggests that evolution used transposable elements to insert modules of transcription factor binding motifs into promoters and, by means of their presence, assemble higher level regulatory networks. In order to explore this question we focused on Alu elements, which are good potential candidates to be part of the building blocks of regulatory networks for two reasons. First, Alu elements are abundant in the upstream region of the TSS of genes, and second, Alu elements contain dozens of putative BSs for TFs. Some of these BSs were found before and their association with Alu was also reported, whereas in some cases although the BSs were found, the fact that they reside on Alu went unnoticed. Finally, we list here also BSs on Alu that were not identified previously. Our findings imply that the biological pathway on which Alu-mediated regulation appears to have the most significant impact is the development process. Many of the TFs that have binding motifs on Alu are associated with development; moreover, some of these BSs were previously demonstrated to be functional in vivo and essential to regulation of some target genes.

TF stands for transcription factors, proteins that bind to specific DNA sequence to activate the process of gene expression.  TSS stands for transcription start site, the precise point at which the copying of the DNA into an RNA format begins.  BS stands for binding site, the region of the DNA that binds with the transcription factors.

You too, p53?

p53 has been called the “Guardian of the genome” and is commonly known as a tumor-suppressor gene – a gene that suppresses the formation of cancer.  Normally, the cell expresses low levels of the p53 protein, but if the genome is damaged, p53 levels rise and in turn activate several programs that will arrest the cell cycle and attempt to repair the DNA damage.  If the genome cannot be repaired, p53 will then activate programmed cell death and the cell will die rather than pass on the damage to future generations.

The Terminator’s Coming

You too, Pax6?

From Novel PAX6 Binding Sites in the Human Genome and the Role of Repetitive Elements in the Evolution of Gene Regulation, by Yi-Hong Zhou, Jessica B. Zheng, Xun Gu, Grady F. Saunders, and W.-K. Alfred Yung.