Scientists show how men amp up their X chromosome

It looks like men have to increase their gene expression to compete with women as they have twice the X chromosomes, sounds a bit unfair to us – Deskarati

Women have two X-chromosomes in their genomes while males have an X and a Y. Gender is defined by that difference, but for men to live, the genetic imbalance must be remedied. In mammals, cells therefore work to emphasize, or “upregulate,” the lone X-chromosome in males and de-emphasize, or “downregulate,” the extra X-chromosome in females.

The means by which males so freely express the genes on their X-chromosomes intrigued Larschan when she was a postdoctoral scholar in the lab of Mitzi Kuroda at Harvard Medical School and Brigham and Women’s Hospital. To figure the process out, she performed experiments in the convenient model of fruitflies. In collaboration with Eric Bishop, a graduate student at Harvard and Boston University, Larschan finished the analysis at Brown, after joining the faculty as assistant professor in January 2010.

The team had a head start. Scientists already suspected that X-chromosome upregulation had a lot to do with a protein complex called MSL that binds to the X-chromosome. MSL stands for “male-specific lethal” because the mutant form would prove deadly for a male fruitfly. What scientists didn’t know was how it worked. It’s not easy to double the levels of expression of a wide variety of genes on one specific chromosome.

It turns out that MSL increases gene expression on the X-chromosome by cracking open the DNA double helix more frequently. In the language of X-chromosome upregulators (a.k.a. men), it’s a specialized drill bit, machined just for the X-chromosome, like a masonry bit is crafted for concrete.

Larschan and her colleagues discovered this by using a technique called “global run-on sequencing” to measure how much of an enzyme called RNA polymerase II was active in the X-chromosome. RNA polymerase II converts DNA instructions into RNA code to express genes. They found that all chromosomes have the same amount of the enzyme, to a point. After that — farther along each gene — the X-chromosome has noticeably more than other chromosomes. In other words, something allows more RNA polymerase II to move farther along the X-chromosome genes, past the point where those

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