It could hold the key to solving problems like hereditary obesity, they say. That's why they're trying to better understand the cellular process that makes calicos look as they do.
Calicos get their orange and black patchwork fur from X chromosome inactivation or "silencing." The cells of Calicos contain two copies of the X chromosome, one from mom and one from dad. But each cell only needs one, so the cells activate one and silence the other -- leading to their varied splashes of color.
Scientists have long understood this, but haven't been able to quite understand how a cell turns off a chromosome without altering the underlying gene structure.
"The inactivation of one out of two X chromosomes in females is an enormously important epigenetic process," said researcher Elizabeth Smith. "Uncovering how only one X chromosome is inactivated will help explain the whole process of epigenetic control, meaning the way changes in gene activity can be inherited without changing the DNA code. It can help answer other questions such as if and how traits like obesity can be passed down through generations."
Smith and her colleagues at the University of California San Francisco have come up with new ways to view the X chromosome while still inside an intact cell -- putting them a step closer to answering some the questions about how gene silencing works. The new imaging technology is called soft x-ray tomography.
"While the structure of the DNA was determined more than 50 years ago, and we're rapidly determining the position of specific genes on chromosomes," Smith explained, "no one had visualized the DNA within an intact nucleus -- an unfixed, hydrated whole cell. We decided to try."
Smith and her research team are presenting the details of their new imaging technique at the 58th Annual Biophysical Society Meeting in San Francisco.
Soft x-ray tomography uses a newly developed microscope with fluorescent probes that can illuminate the inner workings of a cellular nucleus.
"We obtained high-resolution, 3-dimensional views of the intact nucleus and, by using a prototype cryo fluorescence microscope along with the x-ray microscope, we were able to identify one specific chromosome, the inactive X chromosome of female cells," Smith said.
The distribution of body fat is associated with the X chromosome. Learning how to manipulate the way the body reads and translates the instructions from each X chromosome could eventually help scientists turn off, or silence, unfavorable genes -- like ones that encourage obesity.
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