By Shirley Lee

Xist fig1 - samantha

Last year, I decided to add a new member to my family, which at the time consisted of simply yours truly (well, other members of the family do exist but live hundreds of miles from Ann Arbor). After some searching, I brought an orange tabby cat back to my apartment and named her Samantha (pictured at the top). Samantha is a domestic shorthair, with faint mackerel markings along the sides of her body. Her forehead bears the classic “M” pattern characterizing a tabby cat. She also has four stripy legs, pink paw pads, and an orange stripy tail. When I introduced her to my family back home, she wasted no time in conquering everyone with that fuzzy face!

As a new cat owner, I am fascinated with the variety of cats’ coat colors and patterns. Where does the diversity of colors and patterns on different cats come from? Is it only because of the genes inherited from each cat’s parent? Or is there another process at work? As a scientist studying genetics, on the other hand, I am no stranger to the underlying cellular processes that explain this observation. While gene for fur color are part of the story, processes related to epigenetic regulation are important too. They play a major role in how cells control gene functions like coat color. So what exactly is epigenetics?

Imagine a cell in your body, a self-contained compartment approximately one-tenth the thickness of the average human hair and packed full of genetic materials and proteins. The length of human DNA (if you stretch it out from both ends) is about 3 meters long. The cells see a need to stay organized, so they wrap DNA around a group of small proteins called histones, in much the same way you would tie your headphone cables around a cable winder to keep them from getting tangled. These DNA-histone units are called the nucleosomes; a series of nucleosomes are further compacted into a bigger structure called the chromosome.

But how does the cell find frequently needed information in this big DNA jumble? Scientists now understand that epigenetic markers—essentially, sticky notes or bookmarks for the cell’s transcription machinery (this is the genetic information reader)—are all over the chromosomes. Epigenetic markers serve as reminders to a cell for when and where to access its genetic information in response to outside stimulations without actually changing the content of the DNA. Accessing different parts of the genome at different points along the cellular developmental timeline yields the incredible variety of cells found in the body, for example, a liver cell or a hair cell.

Xist fig2 - calico cat

A striking example of epigenetic regulation is X chromosome inactivation (XCI), an important and well-described mechanism in female mammals. Since all female mammals carry two X chromosomes—one from the mother and one from the father—and male mammals only have one X, one X chromosome in a female mammal is randomly inactivated so the cell only receives instructions from one X chromosome. XCI occurs when an RNA fragment, X-inactivation specific transcript (Xist, pronounced as exist), binds and prevents the chromosome from being accessed by transcription machinery, thus silencing it. Therefore a single female organism could have a patch of cells with the paternal X chromosome silenced, and another patch with maternal X chromosomes silenced. Each cell and its descendent cells remember which X chromosome is silenced as the organism grows. Regardless which X chromosome is silenced, the appearance of these cells are indistinguishable on a female human being; but on a female cat, this is reflected in different patches or stripes of coat colors, because those genes are passed down on the X chromosomes.

All of this makes Samantha a special feline, not only from my biased perspective as her owner but also because she is an orange female cat. In addition to being epigenetically regulated, feline coat color is dictated by the rules of genetic inheritance we learned from Mendel. That is to say, in order to be orange, Samantha had to inherit one copy of the orange gene from each parent, an occurrence relatively less common compared to orange male cats (among all orange cats, 20% are female and 80% are male). Whether it was mom’s or dad’s X chromosome that got inactivated, these processes resulted in the existence of this cute, stripy orange feline.

About the author

Shirley is currently a PhD student in Molecular and Cellular Pathology at the University of Michigan. Under the supervision of Dr. Yali Dou, she is searching and developing drug candidates for Mixed Lineage Leukemia (MLL), and simultaneously, trying to understand why things are so complicated in leukemia. Before joining the Dou Lab, Shirley attended the University of Maryland, College Park and got her bachelors in Biochemistry. When not in lab, Shirley enjoys running or training for the next road race, reading, listening to music, and just hanging out with her two rescued cats Samantha and Marco.

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