Showing posts tagged deep sequencing

Engreitz, J. M., Pandya-Jones, A., McDonel, P., Shishkin, A., Sirokman, K., Surka, C., et al. (2013). The Xist lncRNA Exploits Three-Dimensional Genome Architecture to Spread Across the X Chromosome. Science. doi:10.1126/science.1237973

If you ask me, one of the stupidest ideas out there is that of the “Man Cave.” The fact that a mainstream portion of my society thinks that the definition of manhood involves sitting in a specific room and watching TV and burning these remote-control-themed scented candles (or these ones) is nauseating, and I ask you to join me in weeping for the future generations of boy-children who will be raised with this double-whammy addiction to football and fucked-up aromatherapy. 

Scientists (on the whole), like all members of our society, have a truly awful track-record of handling the differences between the sexes. It is depressingly easy to find overwhelming evidence of rampant sexism in how science is practiced on a daily basishow it is taught, and in what it chooses to study and the language it uses to describe those findings. We here at Sick Papes strongly encourage all of you to destroy the Patriarchy and all other forms of inequality (not kidding).

That said, I’ll be DAMNED if there isn’t some seriously dope-ass research out there about some of the (actual) differences between men and women, and X-chromosome inactivation has got be near the top of the Hot column in this century’s “Research Topics: Hot-or-Not” list.

In mammals, XY individuals - those we often call “males” - carry a Y-chromosome, which contains a gene that initiates the cascade of developmental events leading to the growth of a male (including the development of male-specific organ known as the Butt). This is fine (and dandy), but because of this, females have twice as many X chromosomes in every one of their cells, which is not necessarily dandy because twice the chromosome means twice the mRNA levels of every gene on that chromosome, which could really harsh one’s mellow. In order to balance out the amount of transcription from genes on the X-chromosomes, every cell in the embryo of a female mammal shuts down one of the two X-chromosomes, completely silencing its expression. This is X-chromosome inactivation.

Probably the most famous manifestation of X-chromosome inactivation in action is the Calico Cat (editors note: complex internal rhyme unintended). The beautiful colors that besplotch the majestic Calico result from fact that pigmentation genes are located on the X-chromosome. During development, random cells throughout the cat inactivate either one or the other X-chromosome (each of contains a specific pigmentation gene), leading to the differential expression of pigment alleles in random patches of color on the adult’s fur. (Thus, all Calico cats are female, a fact that may surprise some of our readers who don’t already subscribe to Cat Fancy magazine).

The present pape addresses the molecular mechanism by which the X-chromosome shuts down. This process is known to involve a long, non-coding RNA (i.e. it doesn’t encode a protein product, but instead performs its biochemical handjob as an RNA) called Xist. Xist is transcribed from a specific location on the X-chromosome and then, in a bit of particularly trippy biological mystery, spreads to cover the entire chromosome over a period of hours like an iTunes visualizer, correlating with the cessation of transcription.

In this pape, a couple of major players in the game with, from what I can tell, infinity money, developed a technique to do time-lapse, deep-sequencing-based analysis of how the Xist RNA spreads to cover the X-chromosome during the process of X-chromosome inactivation. The first surprising thing is that Xist RNA doesn’t just leak outwards from its source along the length of the chromosome (like, for example, a two-dimensional pee stain on one’s shorts), but rather accumulates in very defined, specific spots across the chromosome (much like, for another example, forming a careful pee pattern in a snowbank). 

The truly sick part of this pape, though, is that the regions where the Xist RNA accumulates are in fact the closest regions of the X chromosome in 3D physical space (not in 2D sequence space)! Because remember: the chromosome is packed into the nucleus like a crazily efficient, unknotted brick of uncooked Ramen noodles, so two points that are physically close in the nucleus may not actually be next to each other along the linear length of the chromosome. The model that the authors propose from their data provides quite heady visuals indeed, and we thank the authors for the opportunity to heartily update our mental imagery of one of the trillions of incredibly small machines working away in our cells.

Contributed by benewencampen
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