X chromosome inactivation in human cells

Published on March 31, 2010 Reviewed on June 29, 2016   48 min

A selection of talks on Cell Biology

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I am Barbara Migeon, a member of the McKusick Nathans Institute of Genetic Medicine at Johns Hopkins. The title of my talk is X Chromosome Inactivation in Human Cell.
I will talk to you about X chromosome inactivation, the way mammals carry out X dosage compensation. This has been the subject of previous talks by Mary Lyon and Jenny Graves. Although we hear a lot about how the mouse inactivates one X chromosome, I will be talking about the version of X chromosome inactivation in our own species. First I will tell you what we know from studies of human cells and human subjects. Then I will talk about how inactivating human X chromosomes differ from the process in other species and what might be responsible for such differences. And last, changing the focus from inactive to active X, I will tell you why diploid human cells have only a single active X, no matter the number of Xs in the cell and how this active X is chosen.
Most studies of the early events in X inactivation have been carried out in mice as it's been difficult to look at human embryos at that time. However, the study of humans has other advantages. Our phenotype is understood better than that of any other organism and we can learn a good deal from the study of cultured cell. Also one X chromosome can be isolated from the other in hybrid cell. Spontaneous abortions provide a wealth of X chromosome deletions and different numbers of X chromosome. And now we have begun to study human ES cells, embryonic stem cells and cleaving embryos left over from in vitro fertilization. We can also transfect human genes into mice for developmental study. Furthermore, the fact that humans are not inbred and are in fact very heterozygous for many X-linked genes has enabled studies less feasible in other mammal. Females are indeed a genetic mosaic as you see here, with some cells expressing the genes from their paternal X, and others, the genes from the maternal one.