The molecular mechanism of X chromosome inactivation

Published on August 31, 2016   38 min

Other Talks in the Series: Epigenetics

0:00
The molecular mechanism of X chromosome inactivation, presented by Professor Neil Brockdorff of the Department of Biochemistry, University of Oxford. I'll begin my talk with a short introduction followed by a discussion of critical steps in the X inactivation process.
0:16
X chromosome inactivation is an important form of epigenetic regulation that evolved in mammals to equalize the levels of expression of genes on the X chromosome, in XX females relative to XY males. Briefly, during early development of a female embryo, each individual cell triggers inactivation of one of the two X chromosomes that are present. The process is normally random. So in an individual cell, there's an equal probability of the X chromosome inherited from the mother or the father being selected as the inactive X. Once X inactivation has occurred, cells remember which of the two X chromosomes was inactivated through all subsequent cell generations. As a consequence, female mammals or chimeras comprised of a mosaic or patchwork of cell populations with either one or the other X chromosome being inactive. A classical illustration of X chromosome inactivation is seen in the coat of the calico cat, which you can see in this image. A gene that gives rise to orange coat color lies on the X chromosome. And calico cats are heterozygous for this gene. The wild type allele encodes black coat color. So when X inactivation occurs in early development, cells either inactivate the chromosome with the wild type gene, giving rise to orange coat color, or the chromosome with the orange gene, giving rise to black coat color. These individual cells then expand into a clonal patch cells during further development, giving rise to these areas with either orange or black coat color.
1:42
X chromosome inactivation results in the transcriptional silencing of genes located on that chromosome. The underlying basis for this process is a change in the state of chromatin, referring to DNA and its associated histone and non-histone proteins. In simplified terms, chromatin can exist either in an open conformation, termed U-chromatin, or a compacted conformation, termed heterochromatin. The inactive X is an example of the latter. This point is illustrated in the image of an interphase nucleus from a female somatic cell, stained with DAPI, a blue-fluorescent dye that binds the DNA. The intense DAPI focus, indicated with the arrow, is the compacted heterochromatic inactive X chromosome. This structure was first observed by Barr and Bertram in 1953 and is sometimes referred to as "The Barr body".
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The molecular mechanism of X chromosome inactivation

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