Xist
Equality of the se-X-es
Calico cat. The patchy distribution of color on calico cats results from the random inactivation of one X chromosome in females.
In mammals, females have two X chromosomes (denoted as XX) whereas males have one X and one Y chromosome. As one can imagine, this would result in the undesirable consequence of doubling the expression of X chromosome genes in females. To prevent this, one of the two X chromosomes is randomly silenced in the cells of females through a process called X chromosome inactivation. This effect can be dramatically seen in Calico cats (picture) where the gene for coat color is located on the X chromosome, resulting in differently colored patches of skin depending on which of the two X chromosomes are inactivated.
Central to the process of X inactivation is the long non-coding RNA Xist, which is also located on the X chromosome. The Xist gene is expressed from the chromosome that is destined to be silenced but not from the active X chromosome. How this choice occurs is largely unknown. In addition, how the Xist RNA acts to recruit silencing factors is also a mystery. As part of our project, we are building synthetic versions of the X inactivation center to study both the regulation of Xist expression as well as various domains within the Xist RNA that are thought to be required for function.
IN COLLABORATION WITH:
Jeannie T. Lee, MD, PhD, Harvard Medical School
Howard Y. Chang, MD, PhD, Stanford University, HHMI
Edith Heard, PhD, European Molecular Biology Laboratory