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Research reveals new understanding of X chromosome inactivation
Date:11/27/2012

Chapel Hill, NC In a paper published in the Nov. 21 issue of Cell, a team led by Mauro Calabrese, a postdoctoral fellow at the University of North Carolina in the lab of Terry Magnuson, chair of the department of genetics and member of the UNC Lineberger Comprehensive Cancer Center, broadens the understanding of how cells regulate silencing of the X chromosome in a process known as X-inactivation.

"This is a classic example of a basic research discovery. X-inactivation is a flagship model for understanding how non-coding RNAs orchestrate large-scale control of gene expression. In the simplest terms, we are trying to understand how cells regulate expression of their genes. Our findings are relevant across the board -- by understanding how normal cells function we can apply that knowledge to similar situations in the understanding and treatment of disease," said Calabrese.

Proper regulation of the X chromosome plays a crucial role in mammalian development. Females inherit a pair of X chromosomes from their parents, and the process of X-inactivation shuts down one of these two Xs.

"Males have XY. Females have two Xs. One of those Xs needs to get shut off. If it does not, it's not compatible with life. It's how we have evolved to equalize doses between males and females," said Calabrese.

While the manner in which the X chromosome is deactivated has been actively studied for 50 years, the exact mechanisms that regulate the process remain a mystery. Calabrese's research used high-throughput sequencing to determine the location and activity of chromosomes with far greater accuracy than previous research.

"Basically, this is using the sequencing technology as a high resolution microscope," said Calabrese.

Under a microscope, the inactive X chromosome (Xi) appears as a cloud-like structure, because it is covered with a non-coding RNA known as Xist. In the traditional model of X-inactivation, genes located i
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Contact: William Davis
william_davis@med.unc.edu
919-962-3405
University of North Carolina Health Care
Source:Eurekalert

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