Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

410 Chapter 7: Control of Gene Expression
Males and females differ in their sex chromosomes. Females have two X chromosomes,
whereas males have one X and one Y chromosome. As a result, female
cells contain twice as many copies of X-chromosome genes as do male cells. In
mammals, the X and Y sex chromosomes differ radically in gene content: the X
chromosome is large and contains more than a thousand genes, whereas the Y
chromosome is small and contains less than 100 genes. Mammals have evolved a
dosage compensation mechanism to equalize the dosage of X-chromosome gene
products between males and females. The correct ratio of X chromosome to autosome
(non-sex chromosome) gene products is carefully controlled, and mutations
that interfere with this dosage compensation are generally lethal.
Mammals achieve dosage compensation by the transcriptional inactivation of
one of the two X chromosomes in female somatic cells, a process known as X-inactivation.
As a result of X-inactivation, two X chromosomes can coexist within
the same nucleus, exposed to the same diffusible transcription regulators, yet differ
entirely in their expression.
Early in the development of a female embryo, when it consists of a few hundred
cells, one of the two X chromosomes in each cell becomes highly condensed
into a type of heterochromatin. The initial choice of which X chromosome to inactivate,
the maternally inherited one (X m ) or the paternally inherited one (X p ), is
random. Once either X p or X m has been inactivated, it remains silent throughout
all subsequent cell divisions of that cell and its progeny, indicating that the
inactive state is faithfully maintained through many cycles of DNA replication and
mitosis. Because X-inactivation is random and takes place after several hundred
cells have already formed in the embryo, every female is a mosaic of clonal groups
of cells in which either X p or X m is silenced (Figure 7–50). These clonal groups are
cell in early embryo
X p
X m
CONDENSATION OF A RANDOMLY
SELECTED X CHROMOSOME
X p X m X p X m
DIRECT INHERITANCE OF THE PATTERN OF CHROMOSOME CONDENSATION
DIRECT INHERITANCE OF THE PATTERN OF CHROMOSOME CONDENSATION
only X m active in this clone
only X p active in this clone
Figure 7–50 X-inactivation. The clonal
inheritance in female mammals of a
condensed, inactive X chromosome.